Differential expression of the semaphorin 3A pathway in prostatic cancer

Abstract

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.

Prostate cancer cells induce osteoblastic differentiation via semaphorin 3A

“…Additionally, NRP1 expression on the membranes of osteoblastic progenitor cells was closely related to the stimulatory level of Sema 3A in the CM of C4-2 cells. Yacoub et al [36] reported similar data showing that expression of membranous NRP1 was strongly associated with Sema 3 A protein levels. Semaphorins and their receptors are widely and differentially expressed in a variety of cancer cells, including prostate, breast, and lung cancers [37], and have well defined roles in cancer growth and metastasis [38,39].…”

Sema3A drastically suppresses tumor growth in oral cancer Xenograft model of mice

“…Previous studies have shown that Sema3A inhibits angiogenesis in prostate cancer [24, 25]. In human squamous cell carcinoma of the tongue, Sema3A amounts are low, with higher expression levels prolonging the survival of patients with oral cancer [21].…”

Expression profiling identifies new function of collapsin response mediator protein 4 as a metastasis-suppressor in prostate cancer

“…VEGF and Sema3A are competitive inhibitors that have overlapping neuropilin-1 binding sites (Miao et al, 1999). A recent study has reported that VEGF and Sema3A, as antagonistic autocrine neuropilin-1 ligands, have a key role in PCa progression (Yacoub et al, 2009). CRMPs can mediate the signal of Sema3A-neuropilins and the expression of CRMPs are positively associated with that of Sema3A (Shih et al, 2001;Deo et al, 2004).…”