MMP9 and melanoma: In early-stage melanoma, G1/S cell cycle arrest and EMT blockade in melanoma cells are induced by normal fibroblasts, thereby suppressing tumor progression.396 Fibroblasts in advanced stages are transformed into CAFs by melanoma-derived exosomes containing miR-155.397,398 A premetastatic microenvironment is formed by CAFs through increased expression of angiogenic factors (VEGFA, FGF2, and MMP-9) via the SOCS1/JAK2/STAT3 signaling pathway, facilitating melanoma metastasis.397 Angiogenesis has been implicated in the metastasis of melanoma.