NFAT1 enhances the effects of tumor-associated macrophages on promoting malignant melanoma growth and metastasis.
NFAT1 enhances the effects of tumor-associated macrophages on promoting malignant melanoma growth and metastasis.
复制标题
NFAT1增强肿瘤相关巨噬细胞促进恶性黑色素瘤生长和转移的作用。
DOI：
10.1042/bsr20181604
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发表时间：
2018
影响因子：
4
通讯作者：
Zhang Jianglin
中科院分区：
文献类型：
--
作者：
Liu Hao;Yang Liping;Qi Min;Zhang Jianglin
肿瘤相关巨噬细胞（tumor associated macrophages, tam）在肿瘤生长、侵袭和转移过程中发挥着重要作用。活化T细胞核因子（NFAT1）已被证明在体内促进黑色素瘤的生长和转移。我们的目的是研究NFAT1是否能够通过影响TAM的特性来促进黑色素瘤的生长和转移。在A375细胞培养的条件培养基中孵育后，从人单核细胞中获得黑色素瘤条件的tam。检测巨噬细胞表型。评估细胞增殖、迁移和侵袭。与正常色素痣组织相比，人恶性黑色素瘤组织CD68+-巨噬细胞浸润和NFAT1表达增加。黑色素瘤条件下的tam表现为m2样表型。黑色素瘤条件下的tam也能促进人类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NFAT1的表达显著增加。在A375和WM451细胞中，NFAT1过表达显著增强了黑色素瘤条件下tam介导的细胞迁移和侵袭的促进作用，而NFAT1敲低则发挥相反的作用。此外，在黑色素瘤条件下的tam中，NFAT1过表达促进了CD68+巨噬细胞浸润、肿瘤生长和体内转移。NFAT1可能在增强tam介导的促进恶性黑色素瘤生长和转移中发挥关键作用。
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 metastasisin 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 metastasisin vivo. NFAT1 may play a critical role in enhancing the TAM-mediated promotion of growth and metastasis in malignant melanoma.