Melanoma-derived exosomes induce reprogramming fibroblasts into cancer-associated fibroblasts via Gm26809 delivery

Cancer-associated fibroblasts (CAFs) are activated fibroblasts and can interact with cancer cells to promote tumor progression. The process of how tumor cells reprogram normal fibroblasts (NFs) to tumor-promoting CAFs regulated by long non-coding RNA (lncRNA) remains incompletely understood. The tumor cells-released exosomes can induce reprogramming of NFs into CAFs. This study aimed to explore the role of melanoma-derived exosomes in regulating NF-CAF transition and to clarify whether lncRNA Gm26809 was involved in this process. The results showed that the exosomes secreted by melanoma cell B16F0 induced reprogramming of fibroblast NIH/3T3 cells into CAFs, as evidenced by increased expression of CAFs markers (alpha-SMA and FAP) and facilitated cell migration. Mechanistically, B16F0-secreted exosome delivered Gm26809 into NIH/3T3 cells where Gm26809 mediated reprogramming of fibroblast NIH/3T3 cells into CAFs. Furthermore, the conditioned medium from the co-culture of NIH/3T3 cells and B16F0-exosomes facilitated cell proliferation and migration in a melanoma cell line (Cloundman S91), and the effect was abrogated by Gm26809 knockdown in B16F0 cells. In summary, melanoma-derived exosomes facilitate melanoma cell proliferation and migration through reprogramming fibroblasts into tumor-promoting CAFs via transferring Gm26809.