{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:10:22Z","timestamp":1753891822277,"version":"3.41.2"},"reference-count":195,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009968","name":"Tiroler Wissenschaftsf\u00f6rderung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Cancer-induced anemia (CIA) is a common consequence of neoplasia and has a multifactorial pathophysiology. The immune response and tumor treatment, both intended to primarily target malignant cells, also affect erythropoiesis in the bone marrow. In parallel, immune activation inevitably induces the iron-regulatory hormone hepcidin to direct iron fluxes away from erythroid progenitors and into compartments of the mononuclear phagocyte system. Moreover, many inflammatory mediators inhibit the synthesis of erythropoietin, which is essential for stimulation and differentiation of erythroid progenitor cells to mature cells ready for release into the blood stream. These pathophysiological hallmarks of CIA imply that the bone marrow is not only deprived of iron as nutrient but also of erythropoietin as central growth factor for erythropoiesis. Tumor-associated macrophages (TAM) are present in the tumor microenvironment and display altered immune and iron phenotypes. On the one hand, their functions are altered by adjacent tumor cells so that they promote rather than inhibit the growth of malignant cells. As consequences, TAM may deliver iron to tumor cells and produce reduced amounts of cytotoxic mediators. Furthermore, their ability to stimulate adaptive anti-tumor immune responses is severely compromised. On the other hand, TAM are potential off-targets of therapeutic interventions against CIA. Red blood cell transfusions, intravenous iron preparations, erythropoiesis-stimulating agents and novel treatment options for CIA may interfere with TAM function and thus exhibit secondary effects on the underlying malignancy. In this Hypothesis and Theory, we summarize the pathophysiological hallmarks, clinical implications and treatment strategies for CIA. Focusing on TAM, we speculate on the potential intended and unintended effects that therapeutic options for CIA may have on the innate immune response and, consequently, on the course of the underlying malignancy.<\/jats:p>","DOI":"10.3389\/fonc.2021.627223","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T05:33:55Z","timestamp":1616650435000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["TAM-ing the CIA\u2014Tumor-Associated Macrophages and Their Potential Role in Unintended Side Effects of Therapeutics for Cancer-Induced Anemia"],"prefix":"10.3389","volume":"11","author":[{"given":"Stefan","family":"Weiler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Nairz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s00520-007-0295-y","article-title":"Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group","volume":"16","author":"Gianni","year":"2008","journal-title":"Support Care Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1914510","article-title":"Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer","volume":"382","author":"Modi","year":"2020","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30355-8","article-title":"Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial","volume":"18","author":"Mody","year":"2017","journal-title":"Lancet Oncol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"8666","DOI":"10.1038\/s41598-018-26811-9","article-title":"The benefits of modified FOLFIRINOX for advanced pancreatic cancer and its induced adverse events: a systematic review and meta-analysis","volume":"8","author":"Tong","year":"2018","journal-title":"Sci Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2004.06.019","article-title":"The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients","volume":"40","author":"Ludwig","year":"2004","journal-title":"Eur J Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2013.01.004","article-title":"Risk of hematologic toxicities in cancer patients treated with sunitinib: a systematic review and meta-analysis","volume":"39","author":"Funakoshi","year":"2013","journal-title":"Cancer Treat Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00892","article-title":"LEAM vs. BEAM vs. CLV Conditioning Regimen for Autologous Stem Cell Transplantation in Malignant Lymphomas. Retrospective Comparison of Toxicity and Efficacy on 222 Patients in the First 100 Days After Transplant, On Behalf of the Romanian Society for Bone Marrow Transplantation","volume":"9","author":"Colita","year":"2019","journal-title":"Front Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817226","article-title":"Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma","volume":"380","author":"Raje","year":"2019","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01294","article-title":"Pathogenesis and Treatment Options of Cancer Related Anemia: Perspective for a Targeted Mechanism-Based Approach","volume":"9","author":"Madeddu","year":"2018","journal-title":"Front Physiol"},{"year":"2017","key":"B11","article-title":"Common Terminology Criteria for Adverse Events"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv348","article-title":"Impaired hepcidin expression in alpha-1-antitrypsin deficiency associated with iron overload and progressive liver disease","volume":"24","author":"Schaefer","year":"2015","journal-title":"Hum Mol Genet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20945","article-title":"IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin","volume":"113","author":"Nemeth","year":"2004","journal-title":"J Clin Invest"},{"key":"B14","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.158.1.420","article-title":"Pathways for the regulation of macrophage iron metabolism by the anti-inflammatory cytokines IL-4 and IL-13","volume":"158","author":"Weiss","year":"1997","journal-title":"J Immunol"},{"key":"B15","article-title":"Induction of hypoferremia and modulation of macrophage iron metabolism by tumor necrosis factor","volume":"61","author":"Alvarez-Hernandez","year":"1989","journal-title":"Lab Invest"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.21037\/atm-20-2037","article-title":"Metabolic reprograming of tumor-associated macrophages","volume":"8","author":"Puthenveetil","year":"2020","journal-title":"Ann Transl Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/0925-5710(96)00475-6","article-title":"Erythropoietin gene expression by hydrogen peroxide","volume":"64","author":"Imagawa","year":"1996","journal-title":"Int J Hematol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1089\/jir.1998.18.555","article-title":"Proinflammatory cytokines lowering erythropoietin production","volume":"18","author":"Jelkmann","year":"1998","journal-title":"J Interferon Cytokine Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.cell.2010.03.014","article-title":"Macrophage diversity enhances tumor progression and metastasis","volume":"141","author":"Qian","year":"2010","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.cmet.2020.03.009","article-title":"Single-Cell RNA Sequencing Maps Endothelial Metabolic Plasticity in Pathological Angiogenesis","volume":"31","author":"Rohlenova","year":"2020","journal-title":"Cell Metab"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00040","article-title":"Hypoxia Pathway Proteins As Central Mediators of Metabolism in the Tumor Cells and Their Microenvironment","volume":"9","author":"Sormendi","year":"2018","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/S0093-7754(01)90211-8","article-title":"Biological consequences of tumor hypoxia","volume":"28","author":"Hockel","year":"2001","journal-title":"Semin Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199006143222401","article-title":"Decreased erythropoietin response in patients with the anemia of cancer","volume":"322","author":"Miller","year":"1990","journal-title":"N Engl J Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/BF02826213","article-title":"Serum erythropoietin level in anemic cancer patients","volume":"17","author":"Ozguroglu","year":"2000","journal-title":"Med Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2008.1.159","article-title":"The anemia of inflammation\/malignancy: mechanisms and management","author":"Adamson","year":"2008","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e20200164","DOI":"10.1084\/jem.20200164","article-title":"IL-33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitors","volume":"217","author":"Swann","year":"2020","journal-title":"J Exp Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.4.989.bloodjournal854989","article-title":"Tumor necrosis factor (TNF)-alpha directly inhibits human erythropoiesis in vitro: role of p55 and p75 TNF receptors","volume":"85","author":"Rusten","year":"1995","journal-title":"Blood"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-04-568451","article-title":"Impact of interferon-gamma on hematopoiesis","volume":"124","author":"de Bruin","year":"2014","journal-title":"Blood"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.06.028","article-title":"Iron attenuates erythropoietin production by decreasing hypoxia-inducible transcription factor 2alpha concentrations in renal interstitial fibroblasts","volume":"94","author":"Suzuki","year":"2018","journal-title":"Kidney Int"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23628","article-title":"Diagnosis and treatment of cancer-related anemia","volume":"89","author":"Gilreath","year":"2014","journal-title":"Am J Hematol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2013.01.001","article-title":"Systemic and cellular consequences of macrophage control of iron metabolism","volume":"24","author":"Recalcati","year":"2013","journal-title":"Semin Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1046","article-title":"Iron and microbial infection","volume":"2","author":"Schaible","year":"2004","journal-title":"Nat Rev Microbiol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01529.x","article-title":"The struggle for iron - a metal at the host-pathogen interface","volume":"12","author":"Nairz","year":"2010","journal-title":"Cell Microbiol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2015.00085","article-title":"Interleukin-22 Signaling in the Regulation of Intestinal Health and Disease","volume":"3","author":"Parks","year":"2015","journal-title":"Front Cell Dev Biol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-351957","article-title":"Hepcidin regulation by innate immune and infectious stimuli","volume":"118","author":"Armitage","year":"2011","journal-title":"Blood"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-06-027631","article-title":"Interleukin-6 induces hepcidin expression through STAT3","volume":"108","author":"Wrighting","year":"2006","journal-title":"Blood"},{"key":"B37","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1053\/j.gastro.2006.10.018","article-title":"STAT3 is required for IL-6-gp130-dependent activation of hepcidin in vivo","volume":"132","author":"Pietrangelo","year":"2007","journal-title":"Gastroenterology"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-03-841197","article-title":"Hepcidin-mediated hypoferremic response to acute inflammation requires a threshold of Bmp6\/Hjv\/Smad signaling","volume":"132","author":"Fillebeen","year":"2018","journal-title":"Blood"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1747","article-title":"Activin B Induces Noncanonical SMAD1\/5\/8 Signaling via BMP Type I Receptors in Hepatocytes: Evidence for a Role in Hepcidin Induction by Inflammation in Male Mice","volume":"157","author":"Canali","year":"2015","journal-title":"Endocrinology"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-02-411470","article-title":"Induction of activin B by inflammatory stimuli up-regulates expression of the iron-regulatory peptide hepcidin through Smad1\/5\/8 signaling","volume":"120","author":"Besson-Fournier","year":"2012","journal-title":"Blood"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-274571","article-title":"In anemia of multiple myeloma, hepcidin is induced by increased bone morphogenetic protein 2","volume":"116","author":"Maes","year":"2010","journal-title":"Blood"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4153","article-title":"Involvement of hepcidin in the anemia of multiple myeloma","volume":"14","author":"Sharma","year":"2008","journal-title":"Clin Cancer Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112802","article-title":"Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis","volume":"367","author":"De Benedetti","year":"2012","journal-title":"N Engl J Med"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e67693","DOI":"10.1371\/journal.pone.0067693","article-title":"Lipocalin-2 expressed in innate immune cells is an endogenous inhibitor of inflammation in murine nephrotoxic serum nephritis","volume":"8","author":"Eller","year":"2013","journal-title":"PloS One"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-2554-7_14","article-title":"The role of cytokines in the regulation of ferritin expression","volume":"356","author":"Rogers","year":"1994","journal-title":"Adv Exp Med Biol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.06.017","article-title":"Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection","volume":"18","author":"Nairz","year":"2015","journal-title":"Cell Host Microbe"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-11-253815","article-title":"Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway","volume":"116","author":"Cohen","year":"2009","journal-title":"Blood"},{"key":"B48","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.162.10.6171","article-title":"Central role of transcription factor NF-IL6 for cytokine and iron-mediated regulation of murine inducible nitric oxide synthase expression","volume":"162","author":"Dlaska","year":"1999","journal-title":"J Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.18.12236","article-title":"Functional requirement of the hypoxia-responsive element in the activation of the inducible nitric oxide synthase promoter by the iron chelator desferrioxamine","volume":"272","author":"Melillo","year":"1997","journal-title":"J Biol Chem"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0802420","article-title":"Pathways for the regulation of interferon-gamma-inducible genes by iron in human monocytic cells","volume":"74","author":"Oexle","year":"2003","journal-title":"J Leukoc Biol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e995047","DOI":"10.4161\/23723556.2014.995047","article-title":"Glutathione peroxidase 4 (Gpx4) and ferroptosis: what\u2019s so special about it","volume":"2","author":"Conrad","year":"2014","journal-title":"Mol Cell Oncol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00992","article-title":"The Role of Ferroptosis in Cancer Development and Treatment Response","volume":"8","author":"Lu","year":"2017","journal-title":"Front Pharmacol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature14344","article-title":"Ferroptosis as a p53-mediated activity during tumour suppression","volume":"520","author":"Jiang","year":"2015","journal-title":"Nature"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2013","journal-title":"Cell"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.01.069","article-title":"Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages","volume":"156","author":"Haldar","year":"2014","journal-title":"Cell"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/nature07472","article-title":"Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis","volume":"457","author":"Kohyama","year":"2009","journal-title":"Nature"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-12-567776","article-title":"Macrophages and iron trafficking at the birth and death of red cells","volume":"125","author":"Korolnek","year":"2014","journal-title":"Blood"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01629","article-title":"Intracellular Ca(2+) Concentration and Phosphatidylserine Exposure in Healthy Human Erythrocytes in Dependence on in vivo Cell Age","volume":"10","author":"Bernhardt","year":"2019","journal-title":"Front Physiol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-386805","article-title":"CD47 functions as a molecular switch for erythrocyte phagocytosis","volume":"119","author":"Burger","year":"2011","journal-title":"Blood"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005351","article-title":"Hemolysis in the spleen drives erythrocyte turnover","volume":"136","author":"Klei","year":"2020","journal-title":"Blood"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4146","article-title":"On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver","volume":"22","author":"Theurl","year":"2016","journal-title":"Nat Med"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13619","article-title":"Hepatic iron overload in the portal tract predicts poor survival in hepatocellular carcinoma after curative resection","volume":"38","author":"Chung","year":"2018","journal-title":"Liver Int"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03112","article-title":"Macrophage Phenotype and Function in Liver Disorder","volume":"10","author":"Dou","year":"2019","journal-title":"Front Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01479","article-title":"Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages","volume":"8","author":"Costa da Silva","year":"2017","journal-title":"Front Immunol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"11326","DOI":"10.1038\/s41598-019-47833-x","article-title":"Iron accumulation in tumor-associated macrophages marks an improved overall survival in patients with lung adenocarcinoma","volume":"9","author":"Thielmann","year":"2019","journal-title":"Sci Rep"},{"key":"B66","doi-asserted-by":"publisher","first-page":"e0166164","DOI":"10.1371\/journal.pone.0166164","article-title":"Intracellular Iron Chelation Modulates the Macrophage Iron Phenotype with Consequences on Tumor Progression","volume":"11","author":"Mertens","year":"2016","journal-title":"PloS One"},{"key":"B67","doi-asserted-by":"publisher","first-page":"e1408751","DOI":"10.1080\/2162402X.2017.1408751","article-title":"Macrophage-derived lipocalin-2 transports iron in the tumor microenvironment","volume":"7","author":"Mertens","year":"2017","journal-title":"Oncoimmunology"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-012-2405-x","article-title":"Ferritin stimulates breast cancer cells through an iron-independent mechanism and is localized within tumor-associated macrophages","volume":"137","author":"Alkhateeb","year":"2013","journal-title":"Breast Cancer Res Treat"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz2193","article-title":"Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis","volume":"369","author":"Chi","year":"2020","journal-title":"Science"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0655-7","article-title":"The iron load of lipocalin-2 (LCN-2) defines its pro-tumour function in clear-cell renal cell carcinoma","volume":"122","author":"Rehwald","year":"2020","journal-title":"Br J Cancer"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.07.015","article-title":"Iron Uptake via DMT1 Integrates Cell Cycle with JAK-STAT3 Signaling to Promote Colorectal Tumorigenesis","volume":"24","author":"Xue","year":"2016","journal-title":"Cell Metab"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/nu9121335","article-title":"The Tumor Suppressor, P53, Decreases the Metal Transporter, ZIP14","volume":"9","author":"Zhao","year":"2017","journal-title":"Nutrients"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042433","article-title":"TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis","volume":"202","author":"Chen","year":"2005","journal-title":"J Exp Med"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1038\/nature13490","article-title":"Functional polarization of tumour-associated macrophages by tumour-derived lactic acid","volume":"513","author":"Colegio","year":"2014","journal-title":"Nature"},{"key":"B75","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/s41556-019-0299-0","article-title":"Extracellular vesicle-packaged HIF-1alpha-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells","volume":"21","author":"Chen","year":"2019","journal-title":"Nat Cell Biol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201064","article-title":"The prolyl hydroxylase PHD3 identifies proinflammatory macrophages and its expression is regulated by activin A","volume":"189","author":"Escribese","year":"2012","journal-title":"J Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-1439","article-title":"Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression","volume":"70","author":"Doedens","year":"2010","journal-title":"Cancer Res"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.11.005","article-title":"Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia-Inducible Factor-1alpha upon LPS Activation in the Presence of Ample Oxygen","volume":"13","author":"Siegert","year":"2015","journal-title":"Cell Rep"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1038\/nature06905","article-title":"NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha","volume":"453","author":"Rius","year":"2008","journal-title":"Nature"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-2555-3_11","article-title":"Role of carbohydrate receptors in the macrophage uptake of dextran-coated iron oxide nanoparticles","volume":"733","author":"Chao","year":"2011","journal-title":"Adv Exp Med Biol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"e25197","DOI":"10.1371\/journal.pone.0025197","article-title":"Different capacity of monocyte subsets to phagocytose iron-oxide nanoparticles","volume":"6","author":"Settles","year":"2011","journal-title":"PloS One"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.250803","article-title":"Intravenous iron preparations transiently generate non-transferrin-bound iron from two proposed pathways","author":"Garbowski","year":"2020","journal-title":"Haematologica"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101611","article-title":"Iron regulates myeloma cell\/macrophage interaction and drives resistance to bortezomib","volume":"36","author":"Camiolo","year":"2020","journal-title":"Redox Biol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfw045","article-title":"Impact of individual intravenous iron preparations on the differentiation of monocytes towards macrophages and dendritic cells","volume":"31","author":"Fell","year":"2016","journal-title":"Nephrol Dial Transplant"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1039\/c8nr03364a","article-title":"Utility of macrophages in an antitumor strategy based on the vectorization of iron oxide nanoparticles","volume":"11","author":"Dalzon","year":"2019","journal-title":"Nanoscale"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfq483","article-title":"Impact of iron treatment on immune effector function and cellular iron status of circulating monocytes in dialysis patients","volume":"26","author":"Sonnweber","year":"2010","journal-title":"Nephrol Dial Transplant"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1797.2009.01174.x","article-title":"Randomized clinical trial on acute effects of i.v. iron sucrose during haemodialysis","volume":"15","author":"Garcia-Fernandez","year":"2010","journal-title":"Nephrol (Carlton)"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.8972","article-title":"Dextrancoated superparamagnetic iron oxide nanoparticles activate the MAPK pathway in human primary monocyte cells","volume":"18","author":"Wu","year":"2018","journal-title":"Mol Med Rep"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S113425","article-title":"Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes","volume":"11","author":"Grosse","year":"2016","journal-title":"Int J Nanomed"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.3109\/17435390.2010.541293","article-title":"Biomedical nanoparticles modulate specific CD4+ T cell stimulation by inhibition of antigen processing in dendritic cells","volume":"5","author":"Blank","year":"2010","journal-title":"Nanotoxicology"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26360","article-title":"USPIO-labeling in M1 and M2-polarized macrophages: An in vitro study using a clinical magnetic resonance scanner","volume":"233","author":"Zini","year":"2018","journal-title":"J Cell Physiol"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4172\/2161-1459.1000223","article-title":"Effects of Anti-repulsive Guidance Molecule C (RGMc\/Hemojuvelin) Antibody on Hepcidin and Iron in Mouse Liver and Tumor Xenografts","volume":"6","author":"Torti","year":"2017","journal-title":"Clin Exp Pharmacol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-345066","article-title":"Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats","volume":"118","author":"Theurl","year":"2011","journal-title":"Blood"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1711031","article-title":"Trial of Tocilizumab in Giant-Cell Arteritis","volume":"377","author":"Stone","year":"2017","journal-title":"N Engl J Med"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0028","article-title":"FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome","volume":"23","author":"Le","year":"2018","journal-title":"Oncologist"},{"key":"B96","doi-asserted-by":"publisher","first-page":"R204","DOI":"10.1186\/ar4397","article-title":"Effect of tocilizumab on haematological markers implicates interleukin-6 signalling in the anaemia of rheumatoid arthritis","volume":"15","author":"Isaacs","year":"2013","journal-title":"Arthritis Res Ther"},{"key":"B97","doi-asserted-by":"publisher","first-page":"R141","DOI":"10.1186\/ar4323","article-title":"Comparative evaluation of the effects of treatment with tocilizumab and TNF-alpha inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid arthritis patients","volume":"15","author":"Song","year":"2013","journal-title":"Arthritis Res Ther"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-009-1075-4","article-title":"Tocilizumab, a humanized anti-interleukin-6 receptor antibody, improved anemia in monkey arthritis by suppressing IL-6-induced hepcidin production","volume":"30","author":"Hashizume","year":"2010","journal-title":"Rheumatol Int"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1002\/art.33496","article-title":"Amplification of the response to Toll-like receptor ligands by prolonged exposure to interleukin-6 in mice: implication for the pathogenesis of macrophage activation syndrome","volume":"64","author":"Strippoli","year":"2012","journal-title":"Arthritis Rheum"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23277","article-title":"Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis","volume":"70","author":"Schulert","year":"2018","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"B101","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s12943-019-0976-4","article-title":"Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis","volume":"18","author":"Wei","year":"2019","journal-title":"Mol Cancer"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1283","article-title":"The Immune-microenvironment Confers Chemoresistance of Colorectal Cancer through Macrophage-Derived IL6","volume":"23","author":"Yin","year":"2017","journal-title":"Clin Cancer Res"},{"key":"B103","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.imbio.2015.11.010","article-title":"Tumor associated macrophages provide the survival resistance of tumor cells to hypoxic microenvironmental condition through IL-6 receptor-mediated signals","volume":"222","author":"Jeong","year":"2015","journal-title":"Immunobiology"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.08.039","article-title":"Tumor-associated macrophages produce interleukin 6 and signal via STAT3 to promote expansion of human hepatocellular carcinoma stem cells","volume":"147","author":"Wan","year":"2014","journal-title":"Gastroenterology"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.031","article-title":"Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling","volume":"155","author":"He","year":"2013","journal-title":"Cell"},{"key":"B106","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.cell.2009.12.052","article-title":"Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression","volume":"140","author":"Park","year":"2009","journal-title":"Cell"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15584","article-title":"Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration","volume":"8","author":"Jayatilaka","year":"2017","journal-title":"Nat Commun"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.11.006","article-title":"Pharmacologic IL-6Ralpha inhibition in cholangiocarcinoma promotes cancer cell growth and survival","volume":"1865","author":"Kleinegger","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-018-0301-9","article-title":"Antiviral activity of bone morphogenetic proteins and activins","volume":"4","author":"Eddowes","year":"2019","journal-title":"Nat Microbiol"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-06-721571","article-title":"Endothelial cells produce bone morphogenetic protein 6 required for iron homeostasis in mice","volume":"129","author":"Canali","year":"2016","journal-title":"Blood"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1038\/ng.335","article-title":"BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism","volume":"41","author":"Andriopoulos","year":"2009","journal-title":"Nat Genet"},{"key":"B112","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4238\/gmr.15017130","article-title":"BMP6 and BMP4 expression in patients with cancer-related anemia and its relationship with hepcidin and s-HJV","volume":"15","author":"Shi","year":"2016","journal-title":"Genet Mol Res"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1080\/16078454.2020.1738098","article-title":"Expression of serum BMP6 and hepcidin in cancer-related anemia","volume":"25","author":"Cheng","year":"2020","journal-title":"Hematology"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13877","article-title":"Targeting the hepcidin-ferroportin pathway in anaemia of chronic kidney disease","volume":"85","author":"Sheetz","year":"2019","journal-title":"Br J Clin Pharmacol"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004653","article-title":"A fully human anti-BMP6 antibody reduces the need for erythropoietin in rodent models of the anemia of chronic disease","volume":"136","author":"Petzer","year":"2019","journal-title":"Blood"},{"key":"B116","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1182\/blood-2018-06-815894","article-title":"Liver iron sensing and body iron homeostasis","volume":"133","author":"Wang","year":"2018","journal-title":"Blood"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0475-x","article-title":"BMP6-induced modulation of the tumor micro-milieu","volume":"38","author":"Stieglitz","year":"2019","journal-title":"Oncogene"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2018.9781","article-title":"Expression of bone morphogenetic protein 6 in non-small cell lung cancer and its significance","volume":"17","author":"Xiong","year":"2018","journal-title":"Oncol Lett"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-08-0226","article-title":"Bone morphogenetic protein 6 (BMP6) and BMP7 inhibit estrogen-induced proliferation of breast cancer cells by suppressing p38 mitogen-activated protein kinase activation","volume":"199","author":"Takahashi","year":"2008","journal-title":"J Endocrinol"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.3892\/or.2019.7275","article-title":"High expression of bone morphogenetic protein (BMP) 6 and BMP7 are associated with higher immune cell infiltration and better survival in estrogen receptorpositive breast cancer","volume":"42","author":"Katsuta","year":"2019","journal-title":"Oncol Rep"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22734","article-title":"Mechanism of pro-tumorigenic effect of BMP-6: neovascularization involving tumor-associated macrophages and IL-1a","volume":"74","author":"Kwon","year":"2014","journal-title":"Prostate"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12206","article-title":"Bone morphogenetic protein-6 induces castration resistance in prostate cancer cells through tumor infiltrating macrophages","volume":"104","author":"Lee","year":"2013","journal-title":"Cancer Sci"},{"key":"B123","doi-asserted-by":"publisher","first-page":"7190546","DOI":"10.1155\/2017\/7190546","article-title":"Different Cytokine and Chemokine Expression Patterns in Malignant Compared to Those in Nonmalignant Renal Cells","author":"Gelbrich","year":"2017","journal-title":"Anal Cell Pathol (Amst)"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-4563","article-title":"BMP-6 in renal cell carcinoma promotes tumor proliferation through IL-10-dependent M2 polarization of tumor-associated macrophages","volume":"73","author":"Lee","year":"2013","journal-title":"Cancer Res"},{"key":"B125","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ph11040135","article-title":"Established and Emerging Concepts to Treat Imbalances of Iron Homeostasis in Inflammatory Diseases","volume":"11","author":"Petzer","year":"2018","journal-title":"Pharm (Basel)"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00160","article-title":"Pharmacological Targeting of the Hepcidin\/Ferroportin Axis","volume":"7","author":"Sebastiani","year":"2016","journal-title":"Front Pharmacol"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.02.064","article-title":"Identification of mutations in SLC40A1 that affect ferroportin function and phenotype of human ferroportin iron overload","volume":"140","author":"Mayr","year":"2011","journal-title":"Gastroenterology"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14539","article-title":"Reduced iron export associated with hepcidin resistance can explain the iron overload spectrum in ferroportin disease","volume":"40","author":"Viveiros","year":"2020","journal-title":"Liver Int"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23377","article-title":"Clinical presentation and molecular pathophysiology of autosomal dominant hemochromatosis caused by a novel ferroportin mutation","volume":"51","author":"Griffiths","year":"2010","journal-title":"Hepatology"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-03-146134","article-title":"The molecular basis of hepcidin-resistant hereditary hemochromatosis","volume":"114","author":"Fernandes","year":"2009","journal-title":"Blood"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07834.x","article-title":"A novel missense mutation in SLC40A1 results in resistance to hepcidin and confirms the existence of two ferroportin-associated iron overload diseases","volume":"147","author":"Letocart","year":"2009","journal-title":"Br J Haematol"},{"key":"B132","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1182\/blood-2017-05-786590","article-title":"Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin","volume":"131","author":"Aschemeyer","year":"2017","journal-title":"Blood"},{"key":"B133","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers12030530","article-title":"The Disturbed Iron Phenotype of Tumor Cells and Macrophages in Renal Cell Carcinoma Influences Tumor Growth","volume":"12","author":"Schnetz","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B134","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/s12885-016-2228-y","article-title":"Local iron homeostasis in the breast ductal carcinoma microenvironment","volume":"16","author":"Marques","year":"2016","journal-title":"BMC Cancer"},{"key":"B135","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1016\/j.cell.2019.10.003","article-title":"Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma","volume":"179","author":"Zhang","year":"2019","journal-title":"Cell"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-330324","article-title":"Ferroportin1 deficiency in mouse macrophages impairs iron homeostasis and inflammatory responses","volume":"118","author":"Zhang","year":"2011","journal-title":"Blood"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.4.2723","article-title":"Attenuated inflammatory responses in hemochromatosis reveal a role for iron in the regulation of macrophage cytokine translation","volume":"181","author":"Wang","year":"2008","journal-title":"J Immunol"},{"key":"B138","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3324\/haematol.2018.197517","article-title":"Macrophage ferroportin is essential for stromal cell proliferation in wound healing","volume":"104","author":"Recalcati","year":"2018","journal-title":"Haematologica"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.3.969","article-title":"Iron regulates nitric oxide synthase activity by controlling nuclear transcription","volume":"180","author":"Weiss","year":"1994","journal-title":"J Exp Med"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121946","article-title":"Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection","volume":"210","author":"Nairz","year":"2012","journal-title":"J Exp Med"},{"key":"B141","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1002\/ajh.25670","article-title":"Oral ferroportin inhibitor VIT-2763: First-in-human, phase 1 study in healthy volunteers","volume":"95","author":"Richard","year":"2020","journal-title":"Am J Hematol"},{"key":"B142","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s13045-017-0427-x","article-title":"A first-in-human phase 1 study of a hepcidin monoclonal antibody, LY2787106, in cancer-associated anemia","volume":"10","author":"Vadhan-Raj","year":"2017","journal-title":"J Hematol Oncol"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-245977","article-title":"Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia","volume":"115","author":"Sasu","year":"2009","journal-title":"Blood"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-456756","article-title":"The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomolgus monkeys","volume":"121","author":"Schwoebel","year":"2012","journal-title":"Blood"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13433","article-title":"Safety, pharmacokinetics and pharmacodynamics of the anti-hepcidin Spiegelmer lexaptepid pegol in healthy subjects","volume":"173","author":"Boyce","year":"2016","journal-title":"Br J Pharmacol"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfs584","article-title":"A hepcidin lowering agent mobilizes iron for incorporation into red blood cells in an adenine-induced kidney disease model of anemia in rats","volume":"28","author":"Sun","year":"2013","journal-title":"Nephrol Dial Transplant"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-740092","article-title":"Momelotinib inhibits ACVR1\/ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents","volume":"129","author":"Asshoff","year":"2016","journal-title":"Blood"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-090019","article-title":"Autocrine formation of hepcidin induces iron retention in human monocytes","volume":"111","author":"Theurl","year":"2008","journal-title":"Blood"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2259","article-title":"TLR4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens","volume":"107","author":"Peyssonnaux","year":"2006","journal-title":"Blood"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.10.025","article-title":"Hepcidin generated by hepatoma cells inhibits iron export from co-cultured THP1 monocytes","volume":"44","author":"Andriopoulos","year":"2006","journal-title":"J Hepatol"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1177\/1010428317717655","article-title":"Upregulation of transferrin receptor-1 induces cholangiocarcinoma progression via induction of labile iron pool","volume":"39","author":"Jamnongkan","year":"2017","journal-title":"Tumour Biol"},{"key":"B152","article-title":"Manipulation of iron transporter genes results in the suppression of human and mouse mammary adenocarcinomas","volume":"30","author":"Jiang","year":"2010","journal-title":"Anticancer Res"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.094060","article-title":"Modulation of iron transport proteins in human colorectal carcinogenesis","volume":"55","author":"Brookes","year":"2006","journal-title":"Gut"},{"key":"B154","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1038\/s41419-019-1854-0","article-title":"Ferroportin downregulation promotes cell proliferation by modulating the Nrf2-miR-17-5p axis in multiple myeloma","volume":"10","author":"Kong","year":"2019","journal-title":"Cell Death Dis"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-3804","article-title":"Decreased ferroportin promotes myeloma cell growth and osteoclast differentiation","volume":"75","author":"Gu","year":"2015","journal-title":"Cancer Res"},{"key":"B156","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.leukres.2019.02.011","article-title":"Low ferroportin expression in AML is correlated with good risk cytogenetics, improved outcomes and increased sensitivity to chemotherapy","volume":"80","author":"Gasparetto","year":"2019","journal-title":"Leuk Res"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-019-0406-1","article-title":"FDA-approved ferumoxytol displays anti-leukaemia efficacy against cells with low ferroportin levels","volume":"14","author":"Trujillo-Alonso","year":"2019","journal-title":"Nat Nanotechnol"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.11.002","article-title":"Disordered signaling governing ferroportin transcription favors breast cancer growth","volume":"27","author":"Chen","year":"2014","journal-title":"Cell Signal"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0243-y","article-title":"Contribution of three-dimensional architecture and tumor-associated fibroblasts to hepcidin regulation in breast cancer","volume":"37","author":"Blanchette-Farra","year":"2018","journal-title":"Oncogene"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.07.029","article-title":"Disordered hepcidin-ferroportin signaling promotes breast cancer growth","volume":"26","author":"Zhang","year":"2014","journal-title":"Cell Signal"},{"key":"B161","doi-asserted-by":"publisher","first-page":"43ra56","DOI":"10.1126\/scisignal.3001127","article-title":"Ferroportin and iron regulation in breast cancer progression and prognosis","volume":"2","author":"Pinnix","year":"2010","journal-title":"Sci Transl Med"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010615)91","article-title":"Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review","volume":"91","author":"Caro","year":"2001","journal-title":"Cancer"},{"key":"B163","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1182\/blood-2018-06-856500","article-title":"Anemia of inflammation","volume":"133","author":"Weiss","year":"2018","journal-title":"Blood"},{"key":"B164","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2014.112813","article-title":"The role of inflammation, iron, and nutritional status in cancer-related anemia: results of a large, prospective, observational study","volume":"100","author":"Maccio","year":"2014","journal-title":"Haematologica"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt118","article-title":"Prevalence of iron deficiency across different tumors and its association with poor performance status, disease status and anemia","volume":"24","author":"Ludwig","year":"2013","journal-title":"Ann Oncol"},{"key":"B166","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPCVZ5B0BOYJGN","article-title":"Using the hemoglobin content of reticulocytes (RET-He) to evaluate anemia in patients with cancer","volume":"142","author":"Peerschke","year":"2014","journal-title":"Am J Clin Pathol"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2013-0031","article-title":"Anemia and iron biomarkers in patients with early breast cancer. Diagnostic value of hepcidin and soluble transferrin receptor quantification","volume":"51","author":"Durigova","year":"2013","journal-title":"Clin Chem Lab Med"},{"key":"B168","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1385\/MO:23:1:23","article-title":"The diagnostic plot: a concept for identifying different states of iron deficiency and monitoring the response to epoetin therapy","volume":"23","author":"Thomas","year":"2006","journal-title":"Med Oncol"},{"key":"B169","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-010-0812-2","article-title":"A new concept for the differential diagnosis and therapy of anaemia in cancer patients","volume":"19","author":"Steinmetz","year":"2010","journal-title":"Support Care Cancer"},{"key":"B170","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.22108","article-title":"Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR\/log ferritin index","volume":"86","author":"Skikne","year":"2011","journal-title":"Am J Hematol"},{"key":"B171","doi-asserted-by":"publisher","DOI":"10.1007\/s10354-016-0505-7","article-title":"Iron deficiency or anemia of inflammation? : Differential diagnosis and mechanisms of anemia of inflammation","volume":"166","author":"Nairz","year":"2016","journal-title":"Wien Med Wochenschr"},{"key":"B172","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.6873","article-title":"Anemia in Hodgkin\u2019s lymphoma: the role of interleukin-6 and hepcidin","volume":"28","author":"Hohaus","year":"2009","journal-title":"J Clin Oncol"},{"key":"B173","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/ejh.12402","article-title":"Hepcidin in tumor-related iron deficiency anemia and tumor-related anemia of chronic disease: pathogenic mechanisms and diagnosis","volume":"94","author":"Shu","year":"2015","journal-title":"Eur J Haematol"},{"key":"B174","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.suronc.2017.01.005","article-title":"Long-term prognostic value of preoperative anemia in patients with colorectal cancer: A systematic review and meta-analysis","volume":"26","author":"Wilson","year":"2017","journal-title":"Surg Oncol"},{"key":"B175","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s12957-015-0488-7","article-title":"T4 stage and preoperative anemia as prognostic factors for the patients with colon cancer treated with adjuvant FOLFOX chemotherapy","volume":"13","author":"An","year":"2015","journal-title":"World J Surg Oncol"},{"key":"B176","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.2005.00719.x","article-title":"Up to 21-day banked red blood cells collected by apheresis and stored for 14 days after automated wash at different times of storage","volume":"90","author":"Grabmer","year":"2006","journal-title":"Vox Sang"},{"key":"B177","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405023111","article-title":"Hemolysis-induced lethality involves inflammasome activation by heme","volume":"111","author":"Dutra","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"B178","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610737200","article-title":"Characterization of heme as activator of Toll-like receptor 4","volume":"282","author":"Figueiredo","year":"2007","journal-title":"J Biol Chem"},{"key":"B179","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2010.05.020","article-title":"Heme Oxygenase-1 expression in M-CSF-polarized M2 macrophages contributes to LPS-induced IL-10 release","volume":"215","author":"Sierra-Filardi","year":"2010","journal-title":"Immunobiology"},{"key":"B180","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131189","article-title":"Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate","volume":"211","author":"Grover","year":"2013","journal-title":"J Exp Med"},{"key":"B181","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406491101","article-title":"Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor","volume":"101","author":"Brines","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"B182","doi-asserted-by":"publisher","first-page":"10379","DOI":"10.1038\/s41598-017-11082-7","article-title":"Erythropoietin enhances Kupffer cell number and activity in the challenged liver","volume":"7","author":"Gilboa","year":"2017","journal-title":"Sci Rep"},{"key":"B183","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-310514","article-title":"Targeting of tumour-infiltrating macrophages via CCL2\/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma","volume":"66","author":"Li","year":"2015","journal-title":"Gut"},{"key":"B184","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26094","article-title":"Recruitment of a myeloid cell subset (CD11b\/Gr1 mid) via CCL2\/CCR2 promotes the development of colorectal cancer liver metastasis","volume":"57","author":"Zhao","year":"2013","journal-title":"Hepatology"},{"key":"B185","doi-asserted-by":"publisher","DOI":"10.1007\/s12565-010-0081-7","article-title":"Erythropoietin-responsive sites in normal and malignant human lung tissues","volume":"85","author":"Yasuda","year":"2010","journal-title":"Anat Sci Int"},{"key":"B186","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-013-9369-2","article-title":"Erythropoietin is involved in the angiogenic potential of bone marrow macrophages in multiple myeloma","volume":"16","author":"De Luisi","year":"2013","journal-title":"Angiogenesis"},{"key":"B187","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s13045-016-0306-x","article-title":"Erythropoietin (EPO)-receptor signaling induces cell death of primary myeloma cells in vitro","volume":"9","author":"Vatsveen","year":"2016","journal-title":"J Hematol Oncol"},{"key":"B188","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000430","article-title":"Identification and transcriptome analysis of erythroblastic island macrophages","volume":"134","author":"Li","year":"2019","journal-title":"Blood"},{"key":"B189","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-013-0544-7","article-title":"Erythropoietin treatment in chemotherapy-induced anemia in previously untreated advanced esophagogastric cancer patients","volume":"19","author":"Thomaidis","year":"2014","journal-title":"Int J Clin Oncol"},{"key":"B190","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.5378","article-title":"Effect of once-weekly epoetin beta on survival in patients with metastatic breast cancer receiving anthracycline- and\/or taxane-based chemotherapy: results of the Breast Cancer-Anemia and the Value of Erythropoietin (BRAVE) study","volume":"26","author":"Aapro","year":"2008","journal-title":"J Clin Oncol"},{"key":"B191","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1093\/annonc\/mdt505","article-title":"Final results from the prospective phase III WSG-ARA trial: impact of adjuvant darbepoetin alfa on event-free survival in early breast cancer","volume":"25","author":"Nitz","year":"2014","journal-title":"Ann Oncol"},{"key":"B192","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2006.06.003","article-title":"Clinical benefits and risks associated with epoetin and darbepoetin in patients with chemotherapy-induced anemia: a systematic review of the literature","volume":"28","author":"Ross","year":"2006","journal-title":"Clin Ther"},{"key":"B193","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djj189","article-title":"Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients","volume":"98","author":"Bohlius","year":"2006","journal-title":"J Natl Cancer Inst"},{"key":"B194","article-title":"Epoetin and Darbopoetin for managing anemia in patients undergoing cancer treatment: Comparative effectiveness update","volume-title":"AHRQ Comparative Effectiveness Reviews","author":"Grant","year":"2013"},{"key":"B195","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003407.pub5","article-title":"Erythropoietin or darbepoetin for patients with cancer","volume":"12","author":"Tonia","year":"2012","journal-title":"Cochrane Database Syst Rev"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.627223\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T23:00:36Z","timestamp":1698102036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.627223\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,25]]},"references-count":195,"alternative-id":["10.3389\/fonc.2021.627223"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2021.627223","relation":{},"ISSN":["2234-943X"],"issn-type":[{"type":"electronic","value":"2234-943X"}],"subject":[],"published":{"date-parts":[[2021,3,25]]},"article-number":"627223"}}