{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:31:13Z","timestamp":1793745073447,"version":"4.6.1"},"reference-count":82,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T00:00:00Z","timestamp":1574640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006827","name":"Florida Department of Health","doi-asserted-by":"publisher","award":["7BC02"],"award-info":[{"award-number":["7BC02"]}],"id":[{"id":"10.13039\/100006827","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Tumor-derived cytokines are known to drive the catabolism of host tissues, including skeletal muscle. However, our understanding of the specific cytokines that initiate this process remains incomplete. In the current study, we conducted multiplex analyte profiling of cytokines in conditioned medium (CM) collected from human pancreatic cancer (PC) cells, human tumor-associated stromal (TAS) cells, and their co-culture. Of the factors identified, interleukin-8 (IL-8) is released at high levels from PC cells and PC\/TAS co-culture and has previously been associated with low muscle mass in cancer patients. We, therefore, treated C2C12 myotubes with IL-8 which led to the activation of ERK1\/2, STAT, and Smad signaling, and induced myotube atrophy. Moreover, the treatment of mice with IL-8 also induced significant muscle wasting, confirming the in vivo relevance of IL-8 on muscle. Mechanistically, IL-8-induced myotube atrophy is inhibited by treatment with the CXCR2 antagonist, SB225002, or by treatment with the ERK1\/2 inhibitor, U0126. We further demonstrate that this axis mediates muscle atrophy induced by pancreatic cancer cell CM, as neutralization of IL-8 or treatment with SB225002 or U0126 significantly inhibit CM-induced myotube atrophy. Thus, these data support a key role of IL-8 released from human PC cells in initiating atrophy of muscle cells via CXCR2-ERK1\/2.<\/jats:p>","DOI":"10.3390\/cancers11121863","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T11:12:21Z","timestamp":1574680341000},"page":"1863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["IL-8 Released from Human Pancreatic Cancer and Tumor-Associated Stromal Cells Signals through a CXCR2-ERK1\/2 Axis to Induce Muscle Atrophy"],"prefix":"10.3390","volume":"11","author":[{"given":"Chandler S.","family":"Callaway","sequence":"first","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea E.","family":"Delitto","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0744-6489","authenticated-orcid":false,"given":"Andrew C.","family":"D\u2019Lugos","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8347-9501","authenticated-orcid":false,"given":"Rachel L.","family":"Nosacka","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Delitto","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Deyhle","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose G.","family":"Trevino","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3974-0247","authenticated-orcid":false,"given":"Sarah M.","family":"Judge","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4488-291X","authenticated-orcid":false,"given":"Andrew R.","family":"Judge","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and classification of cancer cachexia: An international consensus","volume":"12","author":"Fearon","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.clnu.2008.06.013","article-title":"Cachexia: A new definition","volume":"27","author":"Evans","year":"2008","journal-title":"Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6379","DOI":"10.1158\/1078-0432.CCR-07-1147","article-title":"Daily physical-rest activities in relation to nutritional state, metabolism, and quality of life in cancer patients with progressive cachexia","volume":"13","author":"Fouladiun","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17105","DOI":"10.1038\/nrdp.2017.105","article-title":"Cancer-associated cachexia","volume":"4","author":"Baracos","year":"2018","journal-title":"Nat. Rev. Dis Primers"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.21037\/jgo.2017.11.10","article-title":"Cachexia, and not obesity, prior to pancreatic cancer diagnosis worsens survival and is negated by chemotherapy","volume":"9","author":"Hendifar","year":"2018","journal-title":"J. Gastrointest Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1002\/jcsm.12346","article-title":"Tumour-derived leukaemia inhibitory factor is a major driver of cancer cachexia and morbidity in c26 tumour-bearing mice","volume":"9","author":"Kandarian","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4323","DOI":"10.1038\/emboj.2011.292","article-title":"C\/ebpbeta mediates tumour-induced ubiquitin ligase atrogin1\/mafbx upregulation and muscle wasting","volume":"30","author":"Zhang","year":"2011","journal-title":"EMBO J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"MCB-00184","DOI":"10.1128\/MCB.00184-19","article-title":"The toll-like receptor\/myd88\/xbp1 signaling axis mediates skeletal muscle wasting during cancer cachexia","volume":"39","author":"Bohnert","year":"2019","journal-title":"Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41467-017-00726-x","article-title":"Tumor induces muscle wasting in mice through releasing extracellular hsp70 and hsp90","volume":"8","author":"Zhang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00708","DOI":"10.1016\/j.heliyon.2018.e00708","article-title":"Llc tumor cells-derivated factors reduces adipogenesis in co-culture system","volume":"4","author":"Lopes","year":"2018","journal-title":"Heliyon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.mex.2015.02.001","article-title":"Storage conditions and passages alter il-6 secretion in c26 adenocarcinoma cell lines","volume":"2","author":"Norden","year":"2015","journal-title":"MethodsX"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1172\/JCI115767","article-title":"Evidence for the involvement of interleukin 6 in experimental cancer cachexia","volume":"89","author":"Strassmann","year":"1992","journal-title":"J. Clin. Invest."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"R7","DOI":"10.1152\/ajpregu.00738.2001","article-title":"Chemokines and chemokine receptors in leukocyte trafficking","volume":"283","author":"Olson","year":"2002","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S1074-7613(00)80165-X","article-title":"Chemokines: A new classification system and their role in immunity","volume":"12","author":"Zlotnik","year":"2000","journal-title":"Immunity"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.4049\/jimmunol.172.5.2731","article-title":"Of mice and not men: Differences between mouse and human immunology","volume":"172","author":"Mestas","year":"2004","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13058-016-0740-2","article-title":"Tumor-associated stromal cells as key contributors to the tumor microenvironment","volume":"18","author":"Bussard","year":"2016","journal-title":"Breast Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1136\/gutjnl-2011-301220","article-title":"Stellatum: Current consensus and discussion on pancreatic stellate cell research","volume":"61","author":"Erkan","year":"2012","journal-title":"Gut"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hou, Y.C., Wang, C.J., Chao, Y.J., Chen, H.Y., Wang, H.C., Tung, H.L., Lin, J.T., and Shan, Y.S. (2018). Elevated serum interleukin-8 level correlates with cancer-related cachexia and sarcopenia: An indicator for pancreatic cancer outcomes. J. Clin. Med., 7.","DOI":"10.3390\/jcm7120502"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1002\/cncr.11178","article-title":"Elevation of cytokine levels in cachectic patients with prostate carcinoma","volume":"97","author":"Pfitzenmaier","year":"2003","journal-title":"Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/j.clinbiochem.2007.07.013","article-title":"Impact of weight loss on circulating il-1, il-6, il-8, tnf-alpha, vegf-a, vegf-c and midkine in gastroesophageal cancer patients","volume":"40","author":"Matusiewicz","year":"2007","journal-title":"Clin. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1096\/fj.12-222844","article-title":"Diaphragm and ventilatory dysfunction during cancer cachexia","volume":"27","author":"Roberts","year":"2013","journal-title":"FASEB J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jcsm.12307","article-title":"Three cachexia phenotypes and the impact of fat-only loss on survival in folfirinox therapy for pancreatic cancer","volume":"9","author":"Kays","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using david bioinformatics resources","volume":"4","author":"Sherman","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Sherman","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"41114","DOI":"10.1074\/jbc.M400674200","article-title":"Skeletal muscle foxo1 (fkhr) transgenic mice have less skeletal muscle mass, down-regulated type i (slow twitch\/red muscle) fiber genes, and impaired glycemic control","volume":"279","author":"Kamei","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0092-8674(04)00400-3","article-title":"Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy","volume":"117","author":"Sandri","year":"2004","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1096\/fj.11-189977","article-title":"Inhibition of foxo transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy","volume":"26","author":"Reed","year":"2012","journal-title":"FASEB J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Judge, S.M., Wu, C.L., Beharry, A.W., Roberts, B.M., Ferreira, L.F., Kandarian, S.C., and Judge, A.R. (2014). Genome-wide identification of foxo-dependent gene networks in skeletal muscle during c26 cancer cachexia. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-997"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/sj.bjc.6602780","article-title":"Expression of the ubiquitin-proteasome pathway and muscle loss in experimental cancer cachexia","volume":"93","author":"Khal","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"pky043","DOI":"10.1093\/jncics\/pky043","article-title":"Skeletal muscle fibrosis in pancreatic cancer patients with respect to survival","volume":"2","author":"Judge","year":"2018","journal-title":"JNCI Cancer Spectr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2004.09.027","article-title":"Ikkbeta\/nf-kappab activation causes severe muscle wasting in mice","volume":"119","author":"Cai","year":"2004","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E410","DOI":"10.1152\/ajpendo.00039.2012","article-title":"Jak\/stat3 pathway inhibition blocks skeletal muscle wasting downstream of il-6 and in experimental cancer cachexia","volume":"303","author":"Bonetto","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_33","first-page":"E5266","article-title":"Specific targeting of tgf-beta family ligands demonstrates distinct roles in the regulation of muscle mass in health and disease","volume":"114","author":"Chen","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1074\/jbc.271.5.2832","article-title":"Interleukin-8 regulation of the ras\/raf\/mitogen-activated protein kinase pathway in human neutrophils","volume":"271","author":"Knall","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"56375","DOI":"10.18632\/oncotarget.16914","article-title":"Il-8 promotes inflammatory mediators and stimulates activation of p38 mapk\/erk-nf-kappab pathway and reduction of jnk in hnscc","volume":"8","author":"Chan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1158\/1541-7786.MCR-07-0032","article-title":"Interleukin-8 signaling promotes translational regulation of cyclin d in androgen-independent prostate cancer cells","volume":"5","author":"MacManus","year":"2007","journal-title":"Mol. Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.lungcan.2006.11.014","article-title":"Interleukin-8 stimulates cell proliferation in non-small cell lung cancer through epidermal growth factor receptor transactivation","volume":"56","author":"Luppi","year":"2007","journal-title":"Lung Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6868","DOI":"10.1074\/jbc.275.10.6868","article-title":"Chemokine receptors cxcr-1\/2 activate mitogen-activated protein kinase via the epidermal growth factor receptor in ovarian cancer cells","volume":"275","author":"Venkatakrishnan","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Penna, F., Costamagna, D., Fanzani, A., Bonelli, G., Baccino, F.M., and Costelli, P. (2010). Muscle wasting and impaired myogenesis in tumor bearing mice are prevented by erk inhibition. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013604"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1128\/MCB.23.2.543-554.2003","article-title":"The ras\/raf\/mek\/extracellular signal-regulated kinase pathway induces autocrine-paracrine growth inhibition via the leukemia inhibitory factor\/jak\/stat pathway","volume":"23","author":"Park","year":"2003","journal-title":"Mol. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1124\/mol.105.017483","article-title":"Characterization of sis3, a novel specific inhibitor of smad3, and its effect on transforming growth factor-beta1-induced extracellular matrix expression","volume":"69","author":"Jinnin","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14530","DOI":"10.1038\/s41598-017-11978-4","article-title":"Smad3 initiates oxidative stress and proteolysis that underlies diaphragm dysfunction during mechanical ventilation","volume":"7","author":"Tang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11658","DOI":"10.1074\/jbc.M607705200","article-title":"Murine cxcr1 is a functional receptor for gcp-2\/cxcl6 and interleukin-8\/cxcl8","volume":"282","author":"Fan","year":"2007","journal-title":"J. Biol Chem"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1158\/0008-5472.CAN-16-1765","article-title":"Human pancreatic cancer cells induce a myd88-dependent stromal response to promote a tumor-tolerant immune microenvironment","volume":"77","author":"Delitto","year":"2017","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5372","DOI":"10.1158\/0008-5472.CAN-15-3152","article-title":"Differential effects of il6 and activin a in the development of cancer-associated cachexia","volume":"76","author":"Chen","year":"2016","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0304-3835(98)00182-7","article-title":"Tumor growth and food intake in interleukin-6 gene knock-out mice","volume":"132","author":"Molotkov","year":"1998","journal-title":"Cancer Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev.immunol.18.1.217","article-title":"The biology of chemokines and their receptors","volume":"18","author":"Rossi","year":"2000","journal-title":"Annu Rev. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/1043-4666(89)91043-0","article-title":"Interleukin 8 and mcaf: Novel inflammatory cytokines inducible by il 1 and tnf","volume":"1","author":"Matsushima","year":"1989","journal-title":"Cytokine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1084\/jem.173.3.771","article-title":"Phagocytosing neutrophils produce and release high amounts of the neutrophil-activating peptide 1\/interleukin 8","volume":"173","author":"Bazzoni","year":"1991","journal-title":"J. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S0006-291X(88)80364-4","article-title":"Structure determination of a human lymphocyte derived neutrophil activating peptide (lynap)","volume":"151","author":"Gregory","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.4049\/jimmunol.144.6.2223","article-title":"Il-1 alpha or tumor necrosis factor-alpha stimulate release of three nap-1\/il-8-related neutrophil chemotactic proteins in human dermal fibroblasts","volume":"144","author":"Schroder","year":"1990","journal-title":"J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1126\/science.2688092","article-title":"Endothelial interleukin-8: A novel inhibitor of leukocyte-endothelial interactions","volume":"246","author":"Gimbrone","year":"1989","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/sj.onc.1206113","article-title":"Il-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells","volume":"22","author":"Freund","year":"2003","journal-title":"Oncogene"},{"key":"ref_54","first-page":"2290","article-title":"Interleukin 8 expression regulates tumorigenicity and metastasis in human bladder cancer","volume":"60","author":"Inoue","year":"2000","journal-title":"Cancer Res."},{"key":"ref_55","first-page":"93","article-title":"Expression of interleukin-8 correlates with vascularity in human gastric carcinomas","volume":"152","author":"Kitadai","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ctrv.2017.08.004","article-title":"Interleukin-8 in cancer pathogenesis, treatment and follow-up","volume":"60","author":"Alfaro","year":"2017","journal-title":"Cancer Treat. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5697","DOI":"10.1158\/1078-0432.CCR-13-3203","article-title":"Serum interleukin-8 reflects tumor burden and treatment response across malignancies of multiple tissue origins","volume":"20","author":"Sanmamed","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"David, J.M., Dominguez, C., Hamilton, D.H., and Palena, C. (2016). The il-8\/il-8r axis: A double agent in tumor immune resistance. Vaccines, 4.","DOI":"10.3390\/vaccines4030022"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.cyto.2007.11.011","article-title":"Elevation of circulating interleukin-8 is related to lymph node and distant metastases in esophageal squamous cell carcinomas--implication for clinical evaluation of cancer patient","volume":"41","author":"Matusiewicz","year":"2008","journal-title":"Cytokine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.surg.2016.09.038","article-title":"A clinically applicable muscular index predicts long-term survival in resectable pancreatic cancer","volume":"161","author":"Delitto","year":"2017","journal-title":"Surgery"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"29355","DOI":"10.1016\/S0021-9258(18)43882-3","article-title":"The murine interleukin 8 type b receptor homologue and its ligands. Expression and biological characterization","volume":"269","author":"Bozic","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1002\/jlb.64.4.494","article-title":"The murine neutrophil-chemoattractant chemokines lix, kc, and mip-2 have distinct induction kinetics, tissue distributions, and tissue-specific sensitivities to glucocorticoid regulation in endotoxemia","volume":"64","author":"Rovai","year":"1998","journal-title":"J. Leukoc. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1111\/febs.14466","article-title":"A guide to chemokines and their receptors","volume":"285","author":"Hughes","year":"2018","journal-title":"FEBS J."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Cury, S.S., de Moraes, D., Freire, P.P., de Oliveira, G., Marques, D.V.P., Fernandez, G.J., Dal-Pai-Silva, M., Hasimoto, E.N., Dos Reis, P.P., and Rogatto, S.R. (2019). Tumor transcriptome reveals high expression of il-8 in non-small cell lung cancer patients with low pectoralis muscle area and reduced survival. Cancers, 11.","DOI":"10.3390\/cancers11091251"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1073\/pnas.94.7.3052","article-title":"Interleukin 8-stimulated phosphatidylinositol-3-kinase activity regulates the migration of human neutrophils independent of extracellular signal-regulated kinase and p38 mitogen-activated protein kinases","volume":"94","author":"Knall","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.ccr.2012.10.023","article-title":"Jak2\/stat5 inhibition circumvents resistance to pi3k\/mtor blockade: A rationale for cotargeting these pathways in metastatic breast cancer","volume":"22","author":"Britschgi","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6228","DOI":"10.1073\/pnas.092112999","article-title":"Neutrophils are indispensable for hematopoietic stem cell mobilization induced by interleukin-8 in mice","volume":"99","author":"Pruijt","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1172\/JCI117450","article-title":"Long-term impaired neutrophil migration in mice overexpressing human interleukin-8","volume":"94","author":"Simonet","year":"1994","journal-title":"J. Clin. Invest."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1159\/000068146","article-title":"Neutrophil migration across the intestinal epithelial barrier--summary of in vitro data and description of a new transgenic mouse model with doxycycline-inducible interleukin-8 expression in intestinal epithelial cells","volume":"70","author":"Kucharzik","year":"2002","journal-title":"Pathobiology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1053\/j.gastro.2012.09.057","article-title":"Mice that express human interleukin-8 have increased mobilization of immature myeloid cells, which exacerbates inflammation and accelerates colon carcinogenesis","volume":"144","author":"Asfaha","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"7010","DOI":"10.1074\/jbc.M410994200","article-title":"Interleukin-8 induces nuclear transcription factor-kappab through a traf6-dependent pathway","volume":"280","author":"Manna","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"19976","DOI":"10.1074\/jbc.M115.638411","article-title":"A key role for leukemia inhibitory factor in c26 cancer cachexia","volume":"290","author":"Seto","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1016\/j.ajpath.2016.02.009","article-title":"Isolation of pancreatic cancer cells from a patient-derived xenograft model allows for practical expansion and preserved heterogeneity in culture","volume":"186","author":"Pham","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/sj.neo.7900005","article-title":"In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice","volume":"1","author":"Bruns","year":"1999","journal-title":"Neoplasia"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"7214","DOI":"10.1158\/0008-5472.CAN-04-3858","article-title":"Expression and activity of src regulate interleukin-8 expression in pancreatic adenocarcinoma cells: Implications for angiogenesis","volume":"65","author":"Trevino","year":"2005","journal-title":"Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1038\/labinvest.2015.117","article-title":"Primary outgrowth cultures are a reliable source of human pancreatic stellate cells","volume":"95","author":"Han","year":"2015","journal-title":"Lab. Invest."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1096\/fj.01-0866com","article-title":"Activation of an alternative nf-kappab pathway in skeletal muscle during disuse atrophy","volume":"16","author":"Hunter","year":"2002","journal-title":"FASEB J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"8520","DOI":"10.1128\/MCB.25.19.8520-8530.2005","article-title":"Protein kinase d mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species","volume":"25","author":"Storz","year":"2005","journal-title":"Mol. Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/(SICI)1097-0215(19990301)80:5<756::AID-IJC21>3.0.CO;2-N","article-title":"Expression of transforming-growth-factor (tgf)-beta receptors and smad proteins in glioblastoma cell lines with distinct responses to tgf-beta1","volume":"80","author":"Piek","year":"1999","journal-title":"Int. J. Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1128\/MCB.19.2.1401","article-title":"A single amino acid substitution in the v-eyk intracellular domain results in activation of stat3 and enhances cellular transformation","volume":"19","author":"Besser","year":"1999","journal-title":"Mol. Cell Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3836","DOI":"10.1096\/fj.08-110163","article-title":"Hsp70 overexpression inhibits nf-kappab and foxo3a transcriptional activities and prevents skeletal muscle atrophy","volume":"22","author":"Senf","year":"2008","journal-title":"FASEB J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal analysis approaches in Ingenuity Pathway Analysis","volume":"30","author":"Green","year":"2014","journal-title":"Bioinformatics"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/12\/1863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:37:23Z","timestamp":1760189843000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/12\/1863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,25]]},"references-count":82,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["cancers11121863"],"URL":"https:\/\/doi.org\/10.3390\/cancers11121863","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,25]]}}}