Different mechanisms have been described for these effects including (1) secretion of pro-angiogenic factors, like VEGF, bFGF and SDF-1 [49, 88]; (2) surface expression of galectin-1 and podoplanin that upregulate VEGF in cancer cells [89, 90]; (3) activation of TGF-β signaling that triggers angiogenesis by upregulating VEGF expression on CAFs [91]; and (4) ECM remodeling [92]. This evidence concerns the gene CXCL12 and cancer.