In summary, our findings indicate that overexpression of prostate stromal EFNB ligands (EFNB1 and EFNB3) plays a role in PCa tumorigenesis by modulating the TME through alterations in the fibroblast secretome, with multiple effects on neovascularization, collagen deposition, cancer cell proliferation, and migration. This evidence concerns the gene EFNB1 and cancer.