SEMA4A promotes prostate cancer invasion: involvement of tumor microenvironment

Background: Semaphorin 4A (SEMA4A) belonged to a family of membrane-bound proteins that were initially recognized as a kind of axon guidance factors in nervous system. It was preferentially expressed on immune cells and has been proven to play a prominent role in immune function and angiogenesis. Methods and results SEMA4A expression was analyzed by IHC and it’s highly expressed in PCa tissues and correlated with Gleason scores and distant metastasis. SEMA4A could induce Epithelial-mesenchymal transition (EMT) of PCa cells and consequently promote invasion by establishing a positive loop with IL-10 in stromal cells as evidenced by Western blotting and Invasive assay. In vivo studies showed significantly more tumor cell dissemination in mice injected with SEMA4A-overexpressing cells in both mouse models and both the number and size of lung metastases were significantly increased in SEMA4A-overexpressing tumors. SEMA4A depletion by genetic means prevents lung metastasis in PCa xenograft models. Conclusion Our data suggest a crucial role of SEMA4A in PCa and that blockade of SEMA4A- represents an attractive approach to improving therapeutic outcomes.