Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, P.R. China.
College of Life Sciences, Hunan Normal University, Changsha, Hunan Province 410006, P.R. China.
Biosci Rep. 2018 Dec 18;38(6). doi: 10.1042/BSR20181604. Print 2018 Dec 21.
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 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 NFAT1 may play a critical role in enhancing the TAM-mediated promotion of growth and metastasis in malignant melanoma.
肿瘤相关巨噬细胞（TAMs）在肿瘤生长、侵袭和转移中发挥重要作用。核因子活化 T 细胞（NFAT1）已被证明可促进黑色素瘤的生长和转移。我们旨在研究 NFAT1 是否能够通过影响 TAM 特性来促进黑色素瘤的生长和转移。用 A375 细胞培养物的条件培养基孵育人单核细胞后，获得肿瘤相关巨噬细胞（TAMs）。检测巨噬细胞的表型。评估细胞增殖、迁移和侵袭。与正常色素痣组织相比，人类恶性黑色素瘤组织中 CD68-巨噬细胞浸润和 NFAT1 表达增加。肿瘤相关巨噬细胞呈现 M2 样表型。肿瘤相关巨噬细胞还促进人恶性黑色素瘤细胞系 A375 和 WM451 的增殖、迁移和侵袭。此外，与 M0 组相比，TAMs 中的 NFAT1 表达明显增加。NFAT1 过表达显著增强了肿瘤相关巨噬细胞介导的 A375 和 WM451 细胞迁移和侵袭的促进作用，而 NFAT1 敲低则产生相反的效果。此外，肿瘤相关巨噬细胞中 NFAT1 的过表达促进了 CD68-巨噬细胞浸润、肿瘤生长和转移。NFAT1 可能在增强 TAM 介导的恶性黑色素瘤生长和转移中起关键作用。
