{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T20:48:39Z","timestamp":1773694119826,"version":"3.50.1"},"reference-count":37,"publisher":"Portland Press Ltd.","issue":"6","license":[{"start":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T00:00:00Z","timestamp":1564099200000},"content-version":"vor","delay-in-days":220,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,12,21]]},"abstract":"<jats:p>Tumor-associated macrophages (TAMs) play substantial roles in tumor growth, invasion, and metastasis. Nuclear factor of activated T cell (NFAT1) has been shown to promote melanoma growth and metastasis in vivo. We herein aim to investigate whether NFAT1 is capable to promote melanoma growth and metastasis by influencing TAM properties. Melanoma-conditioned TAMs were obtained from human monocytes after incubation with conditioned medium from A375 cell culture. The phenotype of the macrophages was detected. Cell proliferation, migration, and invasion were evaluated. Human malignant melanoma tissues exhibited increased CD68+-macrophage infiltration and NFAT1 expression compared with the normal pigmented nevus tissues. Melanoma-conditioned TAMs displayed M2-like phenotype. Melanoma-conditioned TAMs also promoted proliferation, migration, and invasion of human malignant melanoma cell lines A375 and WM451. Furthermore, NFAT1 expression in TAMs was significantly increased compared with the M0 group. NFAT1 overexpression significantly strengthened the melanoma-conditioned TAM-mediated promotion of cell migration and invasion in A375 and WM451 cells, whereas NFAT1 knockdown exerted the opposite effects. Moreover, NFAT1 overexpression in melanoma-conditioned TAMs promoted CD68+-macrophage infiltration, tumor growth, and metastasis in vivo. NFAT1 may play a critical role in enhancing the TAM-mediated promotion of growth and metastasis in malignant melanoma.<\/jats:p>","DOI":"10.1042\/bsr20181604","type":"journal-article","created":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T17:54:45Z","timestamp":1542736485000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["NFAT1 enhances the effects of tumor-associated macrophages on promoting malignant melanoma growth and metastasis"],"prefix":"10.1042","volume":"38","author":[{"given":"Hao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Hunan Normal University, Changsha, Hunan Province 410006, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5960-1706","authenticated-orcid":false,"given":"Jianglin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2018,12,18]]},"reference":[{"key":"2021111619211722300_B1","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1196\/annals.1371.048","article-title":"Interpreting cancer trends","volume":"1076","author":"Ward","year":"2006","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"2021111619211722300_B2","doi-asserted-by":"publisher","first-page":"35","DOI":"10.2147\/ITT.S134842","article-title":"Melanoma treatment in review","volume":"7","author":"Domingues","year":"2018","journal-title":"Immuno Targets Ther."},{"key":"2021111619211722300_B3","doi-asserted-by":"publisher","first-page":"pii: eaan3311","DOI":"10.1126\/scitranslmed.aan3311","article-title":"T cell-induced CSF1 promotes melanoma resistance to PD1 blockade.","volume":"10","author":"Neubert","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"2021111619211722300_B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.radonc.2016.06.003","article-title":"Radiotherapy and immune checkpoints inhibitors for advanced melanoma","volume":"120","author":"Filippi","year":"2016","journal-title":"Radiother. Oncol."},{"key":"2021111619211722300_B5","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1177\/154411130201300107","article-title":"Dynamics of cell interactions and communications during melanoma development","volume":"13","author":"Li","year":"2002","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"2021111619211722300_B6","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1089\/ars.2012.4617","article-title":"Oxidative stress in malignant melanoma enhances tumor necrosis factor-alpha secretion of tumor-associated macrophages that promote cancer cell invasion","volume":"19","author":"Lin","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"2021111619211722300_B7","doi-asserted-by":"publisher","first-page":"2534","DOI":"10.1159\/000491650","article-title":"Placental Growth Factor Mediates Crosstalk Between Lung Cancer Cells and Tumor-Associated Macrophages in Controlling Cancer Vascularization and Growth","volume":"47","author":"He","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"2021111619211722300_B8","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41419-018-0284-8","article-title":"Loss of NDRG2 in liver microenvironment inhibits cancer liver metastasis by regulating tumor associate macrophages polarization","volume":"9","author":"Li","year":"2018","journal-title":"Cell Death Dis."},{"key":"2021111619211722300_B9","first-page":"1501","article-title":"Gefitinib inhibits M2-like polarization of tumor-associated macrophages in Lewis lung cancer by targeting the STAT6 signaling pathway","volume":"38","author":"Shen","year":"2017","journal-title":"Cell Death Dis."},{"key":"2021111619211722300_B10","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1016\/j.juro.2008.11.090","article-title":"Increased infiltration of tumor associated macrophages is associated with poor prognosis of bladder carcinoma in situ after intravesical bacillus Calmette-Guerin instillation","volume":"179","author":"Takayama","year":"2009","journal-title":"J. Urol."},{"key":"2021111619211722300_B11","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/1471-2407-7-156","article-title":"TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study","volume":"7","author":"Bacman","year":"2007","journal-title":"BMC Cancer"},{"key":"2021111619211722300_B12","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1038\/onc.2013.184","article-title":"Osteopontin signaling upregulates cyclooxygenase-2 expression in tumor-associated macrophages leading to enhanced angiogenesis and melanoma growth via alpha9beta1 integrin","volume":"33","author":"Kale","year":"2014","journal-title":"Oncogene"},{"key":"2021111619211722300_B13","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.jss.2017.09.035","article-title":"Tumor-associated macrophages correlate with phenomenon of epithelial-mesenchymal transition and contribute to poor prognosis in triple-negative breast cancer patients","volume":"222","author":"Zhang","year":"2018","journal-title":"J. Surg. Res."},{"key":"2021111619211722300_B14","doi-asserted-by":"publisher","first-page":"7230","DOI":"10.1158\/1078-0432.CCR-11-1354","article-title":"Tumor-associated macrophages promote angiogenesis and melanoma growth via adrenomedullin in a paracrine and autocrine manner","volume":"17","author":"Chen","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"2021111619211722300_B15","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.coi.2010.01.009","article-title":"Macrophages, innate immunity and cancer: balance, tolerance, and diversity","volume":"22","author":"Mantovani","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"2021111619211722300_B16","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/j.ejca.2006.01.003","article-title":"Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy","volume":"42","author":"Sica","year":"2006","journal-title":"Eur. J. Cancer"},{"key":"2021111619211722300_B17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/271940","article-title":"Macrophages, neutrophils, and cancer: a double edged sword","volume":"2014","author":"Mantovani","year":"2014","journal-title":"New J. Sci."},{"key":"2021111619211722300_B18","doi-asserted-by":"publisher","first-page":"3145","DOI":"10.1158\/0008-5472.CAN-15-2511","article-title":"NFAT1 directly regulates IL-8 and MMP-3 to promote melanoma tumor growth and metastasis","volume":"76","author":"Shoshan","year":"2016","journal-title":"Cancer Res."},{"key":"2021111619211722300_B19","doi-asserted-by":"publisher","first-page":"e66008","DOI":"10.1371\/journal.pone.0066008","article-title":"NFAT1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells","volume":"8","author":"Tie","year":"2013","journal-title":"PLoS ONE"},{"key":"2021111619211722300_B20","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s12935-018-0590-3","article-title":"MiR-98 modulates macrophage polarization and suppresses the effects of tumor-associated macrophages on promoting invasion and epithelial\u2013mesenchymal transition of hepatocellular carcinoma","volume":"18","author":"Li","year":"2018","journal-title":"Cancer Cell Int."},{"key":"2021111619211722300_B21","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1089\/mab.2013.0077","article-title":"An uncoordinated-5 homolog B receptor monoclonal antibody regulates A375 melanoma cell migration","volume":"33","author":"Zuo","year":"2014","journal-title":"Monoclon. Antib. Immunodiagn. Immunother."},{"key":"2021111619211722300_B22","first-page":"1509","article-title":"Long non-coding RNA GAS5 inhibits tumorigenesis via miR-137 in melanoma","volume":"9","author":"Bian","year":"2017","journal-title":"Am. J. Trans. Res."},{"key":"2021111619211722300_B23","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1016\/j.joca.2016.02.003","article-title":"Epigenetically mediated spontaneous reduction of NFAT1 expression causes imbalanced metabolic activities of articular chondrocytes in aged mice","volume":"24","author":"Zhang","year":"2016","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111619211722300_B24","doi-asserted-by":"publisher","first-page":"26194","DOI":"10.1074\/jbc.M109.019836","article-title":"Silencing cAMP-response element-binding protein (CREB) identifies CYR61 as a tumor suppressor gene in melanoma","volume":"284","author":"Dobroff","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2021111619211722300_B25","doi-asserted-by":"publisher","first-page":"5757","DOI":"10.1158\/0008-5472.CAN-12-2424","article-title":"Galectin-3 contributes to melanoma growth and metastasis via regulation of NFAT1 and Autotaxin","volume":"72","author":"Braeuer","year":"2012","journal-title":"Cancer Res."},{"key":"2021111619211722300_B26","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1007\/s00018-014-1796-8","article-title":"Physical and mechanical regulation of macrophage phenotype and function","volume":"72","author":"Mcwhorter","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"2021111619211722300_B27","doi-asserted-by":"publisher","first-page":"3241","DOI":"10.1158\/1078-0432.CCR-16-3122","article-title":"The promise of targeting macrophages in cancer therapy","volume":"23","author":"Brown","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"2021111619211722300_B28","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1167\/iovs.10-5979","article-title":"Detection of M2-macrophages in uveal melanoma and relation with survival","volume":"52","author":"Bronkhorst","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2021111619211722300_B29","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1097\/00008390-200510000-00010","article-title":"Tumour-associated macrophage infiltration, neovascularization and aggressiveness in malignant melanoma: role of monocyte chemotactic protein-1 and vascular endothelial growth factor-A","volume":"15","author":"Varney","year":"2005","journal-title":"Melanoma Res."},{"key":"2021111619211722300_B30","doi-asserted-by":"publisher","first-page":"7230","DOI":"10.1158\/1078-0432.CCR-11-1354","article-title":"Tumor-associated macrophages promote angiogenesis and melanoma growth via adrenomedullin in a paracrine and autocrine manner","volume":"17","author":"Chen","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"2021111619211722300_B31","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1158\/1078-0432.CCR-14-1554","article-title":"BRAF inhibition stimulates melanoma-associated macrophages to drive tumor growth","volume":"21","author":"Wang","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"2021111619211722300_B32","first-page":"123","article-title":"Tumor-associated macrophages as an emerging target against tumors: creating a new path from bench to bedside","volume":"1855","author":"Jinushi","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"2021111619211722300_B33","first-page":"1414","article-title":"Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma","volume":"42","author":"Makitie","year":"2001","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2021111619211722300_B34","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.canlet.2015.03.005","article-title":"Nuclear factor of activated T cells in cancer development and treatment","volume":"361","author":"Shou","year":"2015","journal-title":"Cancer Lett."},{"key":"2021111619211722300_B35","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1007\/s00262-010-0964-4","article-title":"NFAT1 transcription factor is central in the regulation of tissue microenvironment for tumor metastasis","volume":"60","author":"Werneck","year":"2011","journal-title":"Cancer Immunol. Immunother."},{"key":"2021111619211722300_B36","doi-asserted-by":"publisher","first-page":"62","DOI":"10.5732\/cjc.010.10156","article-title":"Expression and unique functions of four nuclear factor of activated T cells isoforms in non-small cell lung cancer","volume":"30","author":"Chen","year":"2011","journal-title":"Chin. J. Cancer"},{"key":"2021111619211722300_B37","doi-asserted-by":"publisher","first-page":"2652","DOI":"10.1038\/jid.2012.179","article-title":"NFATc2 is a potential therapeutic target in human melanoma","volume":"132","author":"Perotti","year":"2012","journal-title":"J. Invest. Dermatol."}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20181604\/809708\/bsr-2018-1604.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20181604\/809708\/bsr-2018-1604.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T20:16:27Z","timestamp":1637093787000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/38\/6\/BSR20181604\/98200\/NFAT1-enhances-the-effects-of-tumor-associated"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,18]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,12,21]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20181604","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,18]]},"article-number":"BSR20181604"}}