Figure 3.

Schematic diagram of tumor-induced activation of fibroblasts and their biological consequences. (a) Conversion of normal fibroblasts into cancer-associated fibroblasts (CAFs) by melanoma-cell-released transforming growth factor-β (TGF-β). (b) CAF-released factors include TGF-β, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), HGF, bone morphogenetic proteins (BMP), vascular endothelial growth factor (VEGF), tumor necrosis factor α (TNFα), interferon γ (IFNγ), CXC-motif-chemokine 12 (CXCL12), interleukin 6 (IL-6), connective tissue growth factor β (CTGFβ), endothelial growth factor (EGF), growth arrest-specific 6 protein (GAS6), galectin-1, secreted frizzled-related protein-1 (SFRP1), sonic hedgehog protein (SHH), neuregulin 1, and fibronectin. These CAF-secreted factors are involved in the modulation of melanoma progression, metastasis, and treatment resistance.