NFAT1 enhances the effects of tumor-associated macrophages on promoting malignant melanoma growth and metastasis

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.