Evaluation of the Effect of Fibroblasts on Melanoma Metastasis Using a Biomimetic Co-Culture Model.

ABSTRACT

Melanoma is a highly malignant tumor originating from melanocytes. The 5-year survival rate of primary melanoma is 98%, whereas the survival rate of metastatic melanoma is only 10%, which can be attributed to the insensitivity to existing treatments. Fibroblasts are the primary cells in the dermis that promote melanoma metastasis; however, the molecular mechanism underlying the fibroblast-melanoma interaction is yet to be completely understood. Herein, gelatin methacryloyl (GelMA) was used to construct a co-culture model for melanoma cells (A375) and fibroblasts. GelMA retains the good biological properties of collagen, which has been identified as the primary component of the melanoma tumor microenvironment. Fibroblasts were encapsulated in GelMA, whereas A375 cells were cultured on the GelMA surface, which realistically mimics the macrostructure of melanoma. A375 cells co-cultured with fibroblasts demonstrated a higher cellular proliferation rate, potentials of neoneurogenesis, overexpression of epithelial mesenchymal transition markers, and a faster migration rate compared with A375 cells cultured alone, which could be due to the cancer-associated fibroblast activation and the overexpression of transforming growth factor ß1 and fibroblast growth factor-2 by fibroblasts. Overall, this study revealed the possible mechanisms of fibroblast-melanoma interaction and suggested that this co-culture model could be potentially further developed as a platform for screening chemotherapies in the future.