Numerous studies indicates that in the secretory epithelial cells of prostate gland, both PSMA and PSA transcriptions are androgen-dependent [39, 40]. The emergence of androgen-insensitive tumor cells arising as a consequence of an adaptation to androgen withdrawal or from pre-existing androgen-independent clone [33]. According to the androgen levels, PSMA and PSA are different

selleck chemicals in several ways. In a previous report Denmeade SR et al, have identified PSMA as a gene that was up-regulated in the more aggressive androgen independent prostate cancer cell line C4-2B compared to the androgen-dependent cell line LNCaP [41]. Recently, in vitro cell-based analysis of PSMA expression was found that both dihydrotestosterone and 1α, 25-dihydroxyvitamin D3 (1, 25-VD) are involved in regulation of this protein [39]. In human PC, the up-regulation of PSMA seems to be a late event in tumor progression as the increase was detected in hormone refractory tumors compared to normal and benign tissue. Authors have also indicate that PSMA is important in very advanced prostate cancer [17, 42]. Unlike PSMA, a loss of expression of tissue PSA has been associated to advanced prostate cancer and to transition into hormone

refractory tumor growth [32, 20]. In addition, several experimental studies have shown that androgen-independent tumors are more angiogenic PF-02341066 cell line than androgen-dependent tumors [43]. Therefore, our finding suggests a possible cross talk between PSMA, PSA and intratumoral angiogenesis and its involvement in tumor growth and metastasis. This relation allowed us to classify the prostate specimens into groups according to the intensity of immunoreactions to CD34. In BPH patients, no differences were found on the intensities of immunoreactions to PSA or to PSMA regarding the levels

of CD34. By contrast, in PC patients depending on the degree of vascularisation, it was found an inverse relation between angiogenesis and PSA. Unlike PSA, the highest intratumoral angiogenesis is accompanied by high PSMA expression in prostate cancer cells. This clearly argues for the view that endothelial cell PSMA expression may be connected with angiogenesis factors production which contribute to neoplastic Osimertinib mouse cell proliferation, motility as well as its contribution to angiogenesis of primary and metastatic cancers [28]. This view is also in line with the study of Tsui P et al, reporting that PSMA expression seems to correlate with vascular endothelial growth factor (VEGF) which stimulates the directed growth of endothelial cells toward malignancies through the process of angiogenesis [44]. The function of PSMA in late prostate cancer is unknown, but its ability to remodel extracellular matrix by proteolytic cleavage might be important.