{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:25:30Z","timestamp":1790717130556,"version":"4.1.0"},"reference-count":89,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:00:00Z","timestamp":1590710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The bone morphogenetic proteins (BMPs), a subgroup of the transforming growth factor-\u03b2 (TGF-\u03b2) superfamily, are involved in multiple biological processes such as embryonic development and maintenance of adult tissue homeostasis. The importance of a functional BMP pathway is underlined by various diseases, including cancer, which can arise as a consequence of dysregulated BMP signaling. Mutations in crucial elements of this signaling pathway, such as receptors, have been reported to disrupt BMP signaling. Next to that, aberrant expression of BMP antagonists could also contribute to abrogated signaling. In this review we set out to highlight how BMP antagonists affect not only the cancer cells, but also the other cells present in the microenvironment to influence cancer progression.<\/jats:p>","DOI":"10.3390\/ijms21113888","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T04:09:03Z","timestamp":1591070943000},"page":"3888","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Extracellular BMP Antagonists, Multifaceted Orchestrators in the Tumor and Its Microenvironment"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0547-1023","authenticated-orcid":false,"given":"Sarah","family":"Ouahoud","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9575-5099","authenticated-orcid":false,"given":"James C.H.","family":"Hardwick","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-9325","authenticated-orcid":false,"given":"Lukas J.A.C.","family":"Hawinkels","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.cytogfr.2005.01.009","article-title":"BMP receptor signaling: Transcriptional targets, regulation of signals, and signaling cross-talk","volume":"16","author":"Miyazono","year":"2005","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Obradovic Wagner, D., Sieber, C., Bhushan, R., B\u00f6rgermann, J.H., Graf, D., and Knaus, P. (2010). BMPs: From Bone to Body Morphogenetic Proteins. Sci. Signal., 3.","DOI":"10.1126\/scisignal.3107mr1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.cytogfr.2009.10.007","article-title":"Recent advances in BMP receptor signaling","volume":"20","author":"Sieber","year":"2009","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.cytogfr.2005.02.007","article-title":"BMP antagonists: Their roles in development and involvement in pathophysiology","volume":"16","author":"Yanagita","year":"2005","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.tcb.2010.01.008","article-title":"Extracellular BMP-antagonist regulation in development and disease: Tied up in knots","volume":"20","author":"Walsh","year":"2010","journal-title":"Trends Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1196\/annals.1346.005","article-title":"BMP and BMP inhibitors in bone","volume":"1068","author":"Rosen","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/cr.2008.302","article-title":"Signaling cross-talk between TGF-\u03b2\/BMP and other pathways","volume":"19","author":"Guo","year":"2009","journal-title":"Cell Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.tcb.2014.12.004","article-title":"BMP signalling: Agony and antagony in the family","volume":"25","author":"Brazil","year":"2015","journal-title":"Trends Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1210\/me.2003-0227","article-title":"Comparative Genomic Analysis of the Eight-Membered Ring Cystine Knot-Containing Bone Morphogenetic Protein Antagonists","volume":"18","author":"Hsueh","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s11154-006-9000-6","article-title":"Bone morphogenetic proteins and their antagonists","volume":"7","author":"Gazzerro","year":"2006","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bbcan.2006.06.004","article-title":"Actions of TGF-\u03b2 as tumor suppressor and pro-metastatic factor in human cancer","volume":"1775","author":"Pardali","year":"2007","journal-title":"Biochim. et Biophys. Acta (Bba)\u2014Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/path.5170","article-title":"Bone morphogenetic protein receptor signal transduction in human disease","volume":"247","author":"Iyengar","year":"2019","journal-title":"J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"78206","DOI":"10.18632\/oncotarget.12151","article-title":"BMP signaling and its paradoxical effects in tumorigenesis and dissemination","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.cell.2010.09.016","article-title":"Intestinal Crypt Homeostasis Results from Neutral Competition between Symmetrically Dividing Lgr5 Stem Cells","volume":"143","author":"Snippert","year":"2010","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1053\/j.gastro.2018.08.016","article-title":"Reserve Stem Cells in Intestinal Homeostasis and Injury","volume":"155","author":"Bankaitis","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/path.2475","article-title":"Gastrointestinal stem cells in development and cancer","volume":"217","author":"Brabletz","year":"2009","journal-title":"J. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1053\/j.gastro.2008.02.059","article-title":"The Bone Morphogenetic Protein Pathway Is Inactivated in the Majority of Sporadic Colorectal Cancers","volume":"134","author":"Kodach","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1126\/science.1093587","article-title":"De Novo Crypt Formation and Juvenile Polyposis on BMP Inhibition in Mouse Intestine","volume":"303","author":"Haramis","year":"2004","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ouahoud, S., Voorneveld, P.W., van der Burg, L.R.A., de Jonge-Muller, E.S.M., Schoonderwoerd, M.J.A., Paauwe, M., de Vos, T., de Wit, S., van Pelt, G.W., and Mesker, W.E. (2020). Bidirectional tumor\/stroma crosstalk promotes metastasis in mesenchymal colorectal cancer. Oncogene.","DOI":"10.1038\/s41388-020-1157-z"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/nm.2328","article-title":"Why don\u2019t we get more cancer? A proposed role of the microenvironment in restraining cancer progression","volume":"17","author":"Bissell","year":"2011","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/nm.3394","article-title":"Microenvironmental regulation of tumor progression and metastasis","volume":"19","author":"Quail","year":"2013","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nrc2618","article-title":"Microenvironmental regulation of metastasis","volume":"9","author":"Joyce","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nature03096","article-title":"Stromal fibroblasts in cancer initiation and progression","volume":"432","author":"Bhowmick","year":"2004","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/ng.2263","article-title":"Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1","volume":"44","author":"Jaeger","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s10689-018-0090-6","article-title":"Identification of a novel GREM1 duplication in a patient with multiple colon polyps","volume":"18","author":"McKenna","year":"2019","journal-title":"Fam. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.bone.2005.07.015","article-title":"Overexpression of noggin inhibits BMP-mediated growth of osteolytic prostate cancer lesions","volume":"38","author":"Feeley","year":"2006","journal-title":"Bone"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1359\/jbmr.060706","article-title":"Mixed Metastatic Lung Cancer Lesions in Bone Are Inhibited by Noggin Overexpression and Rank:Fc Administration","volume":"21","author":"Feeley","year":"2006","journal-title":"J. Bone Miner. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1073\/pnas.0237312100","article-title":"Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad\/estrogen receptor crosstalk","volume":"100","author":"Giacomini","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8276","DOI":"10.1158\/0008-5472.CAN-04-2251","article-title":"Bone Morphogenetic Protein (BMP)-6 Signaling and BMP Antagonist Noggin in Prostate Cancer","volume":"64","author":"Haudenschild","year":"2004","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1093\/carcin\/bgg100","article-title":"The mature bone morphogenetic protein-2 is aberrantly expressed in non-small cell lung carcinomas and stimulates tumor growth of A549 cells","volume":"24","author":"Langenfeld","year":"2003","journal-title":"Carcinogenesis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1158\/0008-5472.CAN-03-1382","article-title":"Vascular Endothelial Growth Factor Contributes to the Prostate Cancer-Induced Osteoblast Differentiation Mediated by Bone Morphogenetic Protein","volume":"64","author":"Dai","year":"2004","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1158\/1541-7786.141.2.3","article-title":"Bone Morphogenetic Protein-2 Stimulates Angiogenesis in Developing Tumors","volume":"2","author":"Langenfeld","year":"2004","journal-title":"Mol. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1096\/fj.05-4126com","article-title":"Chordin is underexpressed in ovarian tumors and reduces tumor cell motility","volume":"20","author":"Moll","year":"2006","journal-title":"FASEB J."},{"key":"ref_34","first-page":"2331","article-title":"The BMP antagonist, SOSTDC1, restrains gastric cancer progression via inactivation of c-Jun signaling","volume":"9","author":"Cui","year":"2019","journal-title":"Am. J. Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13578-016-0091-9","article-title":"SOSTDC1 is down-regulated in non-small cell lung cancer and contributes to cancer cell proliferation","volume":"6","author":"Liu","year":"2016","journal-title":"Cell Biosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.str.2013.06.005","article-title":"Structure of protein related to Dan and Cerberus: Insights into the mechanism of bone morphogenetic protein antagonism","volume":"21","author":"Nolan","year":"2013","journal-title":"Structure"},{"key":"ref_37","first-page":"199","article-title":"Gremlin 2 is Repressed in Invasive Endometrial Cancer and Inhibits Cell Growth In Vitro","volume":"36","author":"Tsubamoto","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1080\/15384101.2019.1646561","article-title":"GREM2 maintains stem cell-like phenotypes in gastric cancer cells by regulating the JNK signaling pathway","volume":"18","author":"Ran","year":"2019","journal-title":"Cell Cycle"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1016\/j.cellsig.2007.03.008","article-title":"Proinvasive activity of BMP-7 through SMAD4 \/src -independent and ERK\/ Rac \/JNK -dependent signaling pathways in colon cancer cells","volume":"19","author":"Grijelmo","year":"2007","journal-title":"Cell. Signal."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/annonc\/mdm453","article-title":"Bone morphogenetic protein 7 expression associates with bone metastasis in breast carcinomas","volume":"19","author":"Alarmo","year":"2008","journal-title":"Ann. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.canlet.2009.02.046","article-title":"Overexpression of bone morphogenetic protein 4 enhances the invasiveness of Smad4-deficient human colorectal cancer cells","volume":"281","author":"Deng","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/S0016-5085(99)70024-7","article-title":"Bone morphogenetic protein 2 exerts diverse effects on cell growth in vitro and is expressed in human pancreatic cancer in vivo","volume":"116","author":"Kleeff","year":"1999","journal-title":"Gastroenterology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1053\/j.gastro.2014.03.052","article-title":"Loss of SMAD4 Alters BMP Signaling to Promote Colorectal Cancer Cell Metastasis via Activation of Rho and ROCK","volume":"147","author":"Voorneveld","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4887","DOI":"10.1038\/s41388-019-0765-y","article-title":"Biological heterogeneity and versatility of cancer-associated fibroblasts in the tumor microenvironment","volume":"38","author":"Bu","year":"2019","journal-title":"Oncogene"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41568-019-0238-1","article-title":"A framework for advancing our understanding of cancer-associated fibroblasts","volume":"20","author":"Sahai","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14842","DOI":"10.1073\/pnas.0606857103","article-title":"Bone morphogenetic protein antagonist gremlin 1 is widely expressed by cancer-associated stromal cells and can promote tumor cell proliferation","volume":"103","author":"Sneddon","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.humpath.2016.12.018","article-title":"Prognostic significance of stromal GREM1 expression in colorectal cancer","volume":"62","author":"Jang","year":"2017","journal-title":"Hum. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13058-019-1194-0","article-title":"Cancer-associated fibroblast-derived Gremlin 1 promotes breast cancer progression","volume":"21","author":"Ren","year":"2019","journal-title":"Breast Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4741","DOI":"10.1038\/onc.2010.215","article-title":"EMT, cancer stem cells and drug resistance: An emerging axis of evil in the war on cancer","volume":"29","author":"Singh","year":"2010","journal-title":"Oncogene"},{"key":"ref_50","first-page":"11","article-title":"Gremlin Activates the Smad Pathway Linked to Epithelial Mesenchymal Transdifferentiation in Cultured Tubular Epithelial Cells","volume":"2014","author":"Lavoz","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Namkoong, H., Shin, S.M., Kim, H.K., Ha, S.-A., Cho, G.W., Hur, S.Y., Kim, T.E., and Kim, J.W. (2006). The bone morphogenetic protein antagonist gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein. BMC Cancer, 6.","DOI":"10.1186\/1471-2407-6-74"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"575","DOI":"10.2353\/ajpath.2010.090442","article-title":"Prognostic Significance of Gremlin1 (GREM1) Promoter CpG Island Hypermethylation in Clear Cell Renal Cell Carcinoma","volume":"176","author":"Baldewijns","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1038\/oncsis.2013.29","article-title":"Gremlin-1 associates with fibrillin microfibrils in vivo and regulates mesothelioma cell survival through transcription factor slug","volume":"2","author":"Tamminen","year":"2013","journal-title":"Oncogenesis"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00535-012-0614-z","article-title":"Expression of gremlin 1 correlates with increased angiogenesis and progression-free survival in patients with pancreatic neuroendocrine tumors","volume":"48","author":"Chen","year":"2013","journal-title":"J. Gastroenterol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1101\/gad.235515.113","article-title":"Glioma cancer stem cells secrete Gremlin1 to promote their maintenance within the tumor hierarchy","volume":"28","author":"Yan","year":"2014","journal-title":"Genes Dev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"98280","DOI":"10.18632\/oncotarget.21550","article-title":"Gremlin-1 is a key regulator of the invasive cell phenotype in mesothelioma","volume":"8","author":"Yin","year":"2017","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s12964-019-0467-7","article-title":"GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients","volume":"17","author":"Neckmann","year":"2019","journal-title":"Cell Commun. Signal."},{"key":"ref_58","first-page":"1367","article-title":"Neural crest cell migration of mouse B16-F1 melanoma cells transplanted into the chick embryo is inhibited by the BMP-antagonist noggin","volume":"31","author":"Busch","year":"2007","journal-title":"Int. J. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/labinvest.2008.55","article-title":"Aggressive melanoma cells escape from BMP7-mediated autocrine growth inhibition through coordinated Noggin upregulation","volume":"88","author":"Hsu","year":"2008","journal-title":"Lab. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.2353\/ajpath.2009.090163","article-title":"Bone morphogenetic protein antagonist noggin promotes skin tumorigenesis via stimulation of the Wnt and Shh signaling pathways","volume":"175","author":"Sharov","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.bone.2008.09.009","article-title":"Influence of simultaneous targeting of the bone morphogenetic protein pathway and RANK\/RANKL axis in osteolytic prostate cancer lesion in bone","volume":"44","author":"Virk","year":"2009","journal-title":"Bone"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Secondini, C., Wetterwald, A., Schwaninger, R., Thalmann, G.N., and Cecchini, M.G. (2011). The role of the BMP signaling antagonist noggin in the development of prostate cancer osteolytic bone metastasis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016078"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"21346","DOI":"10.1074\/jbc.M112.355834","article-title":"Identification of NOG as a Specific Breast Cancer Bone Metastasis-supporting Gene","volume":"287","author":"Tarragona","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1242\/dev.01251","article-title":"Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis","volume":"131","author":"Michos","year":"2004","journal-title":"Development"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"15418","DOI":"10.1073\/pnas.0707210104","article-title":"Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors","volume":"104","author":"Kosinski","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Karagiannis, G., Musrap, N., Saraon, P., Treacy, A., Schaeffer, D.F., Kirsch, R., Riddell, R.H., and Diamandis, E.P. (2015). Bone morphogenetic protein antagonist gremlin-1 regulates colon cancer progression. Biol. Chem., 163\u2013183.","DOI":"10.1515\/hsz-2014-0221"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/nrc3500","article-title":"Beyond TGF\u03b2: Roles of other TGF\u03b2 superfamily members in cancer","volume":"13","author":"Wakefield","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.diff.2009.08.009","article-title":"Exploration of Shh and BMP paracrine signaling in a prostate cancer xenograft","volume":"79","author":"Shaw","year":"2010","journal-title":"Differentiation"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"66ra65","DOI":"10.1126\/scitranslmed.3001542","article-title":"Stromal Endothelial Cells Directly Influence Cancer Progression","volume":"3","author":"Franses","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nrc.2017.51","article-title":"Microenvironmental regulation of tumour angiogenesis","volume":"17","author":"Biziato","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1182\/blood-2006-06-032276","article-title":"Bone morphogenic protein antagonist Drm\/gremlin is a novel proangiogenic factor","volume":"109","author":"Stabile","year":"2006","journal-title":"Blood"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1182\/blood-2007-09-111450","article-title":"Angiopoietin-1 mediates the proangiogenic activity of the bone morphogenic protein antagonist Drm","volume":"112","author":"Mitola","year":"2008","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1182\/blood-2010-06-291930","article-title":"Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2","volume":"116","author":"Mitola","year":"2010","journal-title":"Blood"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"35353","DOI":"10.18632\/oncotarget.9286","article-title":"Monomeric gremlin is a novel vascular endothelial growth factor receptor-2 antagonist","volume":"7","author":"Grillo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1365-2567.2007.02541.x","article-title":"Bone morphogenetic protein-2\/4 signalling pathway components are expressed in the human thymus and inhibit early T-cell development","volume":"121","author":"Cejalvo","year":"2007","journal-title":"Immunology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5496","DOI":"10.4049\/jimmunol.169.10.5496","article-title":"Bone Morphogenetic Protein 2\/4 Signaling Regulates Early Thymocyte Differentiation","volume":"169","author":"Outram","year":"2002","journal-title":"J. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1182\/blood-2011-07-370650","article-title":"Expression of BMPRIA on human thymic NK cell precursors: Role of BMP signaling in intrathymic NK cell development","volume":"119","author":"Hidalgo","year":"2012","journal-title":"Blood"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5429","DOI":"10.1111\/jcmm.13814","article-title":"BMP-2 induces human mononuclear cell chemotaxis and adhesion and modulates monocyte-to-macrophage differentiation","volume":"22","author":"Pardali","year":"2018","journal-title":"J. Cell Mol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/eji.201343693","article-title":"Autocrine activation of canonical BMP signaling regulates PD-L1 and PD-L2 expression in human dendritic cells","volume":"44","author":"Hidalgo","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nri.2016.112","article-title":"Immunoregulation by members of the TGF\u03b2 superfamily","volume":"16","author":"Chen","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.biocel.2011.12.013","article-title":"A portrait of Transforming Growth Factor \u03b2 superfamily signalling: Background matters","volume":"44","author":"Horbelt","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/path.4537","article-title":"Gremlin regulates renal inflammation via the vascular endothelial growth factor receptor 2 pathway","volume":"236","author":"Lavoz","year":"2015","journal-title":"J. Pathol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/ATVBAHA.113.302517","article-title":"Cyclic Adenosine Monophosphate-Response Element\u2013Binding Protein Mediates the Proangiogenic or Proinflammatory Activity of Gremlin","volume":"34","author":"Corsini","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1042\/CS20171553","article-title":"Gremlin activates the Notch pathway linked to renal inflammation","volume":"132","author":"Lavoz","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"31635","DOI":"10.1074\/jbc.M113.477745","article-title":"Gremlin-1 Is an Inhibitor of Macrophage Migration Inhibitory Factor and Attenuates Atherosclerotic Plaque Growth in ApoE\u2212\/\u2212 Mice","volume":"288","author":"Schneider","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5914","DOI":"10.4049\/jimmunol.173.10.5914","article-title":"Cutting Edge: Bone Morphogenetic Protein Antagonists Drm\/Gremlin and Dan Interact with Slits and Act as Negative Regulators of Monocyte Chemotaxis","volume":"173","author":"Chen","year":"2004","journal-title":"J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1002\/art.21897","article-title":"Noggin haploinsufficiency differentially affects tissue responses in destructive and remodeling arthritis","volume":"54","author":"Lories","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"H747","DOI":"10.1152\/ajpheart.00825.2012","article-title":"The bone morphogenic protein inhibitor, noggin, reduces glycemia and vascular inflammation in db\/db mice","volume":"305","author":"Koga","year":"2013","journal-title":"Am. J. Physiol. -Heart Circ. Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Whiteside, T. (2013). Immune Responses to Cancer: Are They Potential Biomarkers of Prognosis?. Front. Oncol., 3.","DOI":"10.3389\/fonc.2013.00107"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/11\/3888\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:33:52Z","timestamp":1760175232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/11\/3888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,29]]},"references-count":89,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["ijms21113888"],"URL":"https:\/\/doi.org\/10.3390\/ijms21113888","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,29]]}}}