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Regulatory T Cells Induce Metastasis by Activating Tgf-Β and Enhancing the Epithelial–Mesenchymal Transition

by Eonju Oh 1, JinWoo Hong 1 and Chae-Ok Yun 1,2,*
1
Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea
2
Institute of Nano Science and Technology (INST), Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea
*
Author to whom correspondence should be addressed.
Cells 2019, 8(11), 1387; https://doi.org/10.3390/cells8111387
Received: 4 October 2019 / Revised: 29 October 2019 / Accepted: 31 October 2019 / Published: 4 November 2019
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-β (TGF-β) 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-β and mesenchymal markers is important for augmenting the migration capacity and invasiveness of melanoma, thereby contributing to the metastasis.
Keywords: melanoma; cancer metastasis; epithelial–mesenchymal transition; TGF-β; regulatory T cells melanoma; cancer metastasis; epithelial–mesenchymal transition; TGF-β; regulatory T cells
MDPI and ACS Style

Oh, E.; Hong, J.; Yun, C.-O. Regulatory T Cells Induce Metastasis by Activating Tgf-Β and Enhancing the Epithelial–Mesenchymal Transition. Cells 2019, 8, 1387.

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