Differential expression of the semaphorin 3A pathway in prostatic cancer

Aims: To analyse the expression pattern of the semaphorin 3A (Sema3A) pathway, including the receptor neuropilin 1 (NRP1) and its ligands the 'antitumoral' Sema3A and the 'protumoral' vascular endothelial growth factor (VEGF) in prostatic cancer. Methods and results: tissues were obtained from 120 patients treated by prostatectomy for clinically localized prostatic cancer, and 31 hormone-refractory prostatic cancer (HRPC) samples. Immunohistochemistry was performed on tissue microarrays using antibodies directed against Sema3A, NRP1 and VEGF. Moreover, real-time reverse transcriptase-polymerase chain reaction was performed on frozen prostatic tissue, including normal prostate, clinically localized tumours and HPRC. Sema3A immunoreactivity of the membrane of cancer cells was closely associated with NRP1 expression in clinically localized prostatic cancer, but not in HRPC. In clinically localized cancer, Sema3A expression correlated with lower preoperative prostate-specific antigen (PSA) and pathological stage; NRP1 reactivity was associated with lower PSA and Gleason score, and VEGF reactivity with higher PSA and Gleason score. HRPC displayed higher expression of NRP1 compared with clinically localized cancer, and lower Sema3A immunoreactivity. Conclusions: These results support the hypothesis that dysregulation of the Sema3A pathway plays a key role in prostatic cancer progression, and suggest a loss of the inhibitory Sema3A autocrine loop in HRPC.