{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:14:09Z","timestamp":1792012449744,"version":"4.4.0"},"reference-count":73,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T00:00:00Z","timestamp":1572825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002380","name":"Hanyang University","doi-asserted-by":"publisher","award":["HY-2011-G-201100000001880"],"award-info":[{"award-number":["HY-2011-G-201100000001880"]}],"id":[{"id":"10.13039\/501100002380","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Malignant melanoma is the most aggressive form of skin cancer; a substantial percentage of patients present with distant metastases. However, the mechanism of metastasis is not well understood. Here, we demonstrate that the administration of exogenous regulatory T cells (Tregs) into melanoma tumor-bearing mice results in a significant increase in lung metastasis. An increase in the invasive and metastatic phenotype of melanoma was mediated by cell-to-cell contact between melanoma cells and Tregs, which elevated the expression level of transforming growth factor-\u03b2 (TGF-\u03b2) and the subsequent induction of the epithelial-to-mesenchymal transition (EMT). B16-BL6 melanoma tumors co-cultured with Tregs showed a larger population of migrating cells compared to B16-BL6 tumors cultured without Tregs. Additionally, the injection of exogenous Tregs into B16-BL6 melanoma tumors led to the recruitment and infiltration of endogenous Tregs into tumor tissues, thus increasing the overall Treg percentage in the tumor infiltrating lymphocyte population. Collectively, our findings propose novel mechanisms in which exogenous Treg-dependent upregulation of TGF-\u03b2 and mesenchymal markers is important for augmenting the migration capacity and invasiveness of melanoma, thereby contributing to the metastasis.<\/jats:p>","DOI":"10.3390\/cells8111387","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T10:49:07Z","timestamp":1572864547000},"page":"1387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Regulatory T Cells Induce Metastasis by Increasing Tgf-\u03b2 and Enhancing the Epithelial\u2013Mesenchymal Transition"],"prefix":"10.3390","volume":"8","author":[{"given":"Eonju","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JinWoo","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae-Ok","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea"},{"name":"Institute of Nano Science and Technology (INST), Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.lfs.2017.02.011","article-title":"Towards therapeutic advances in melanoma management: An overview","volume":"174","author":"Singh","year":"2017","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3635","DOI":"10.1200\/JCO.2001.19.16.3635","article-title":"Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma","volume":"19","author":"Balch","year":"2001","journal-title":"J. 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