Ben Jemaa et al. Journal of Experimental & Clinical Cancer Research 2010, 29:171 http://www.jeccr.com/content/29/1/171 Page 7 of 9 Figure 4 Percentage of prostatic specimens with positive or negative immunoreactions to PSA and PSMA according to groups: normal prostate (NP), benign prostatic hyperplasia (BPH) and prostatic carcinoma (PC). Statistical analysis refers to each group separately at p≤0.05. both normal and prostate cancer tissue. These data sug- gest that these markers are regulated differentially in their expression and this difference seems to increase with malignant transformation [34]. The preponderance of PSMA or PSA expression in each prostatic subgroup depends on the cellular context. The heterogeneity of PSMA versus PSA expression under the same sub-group of prostate-associated profiles is, in part, thought to be due to the effect of androgen, cytokines, growth factors receptors, adhesion molecules and many other mem- brane-generated signals that all share the ability to effi- ciently regulate PSMA and PSA gene expression [37,28,38]. Numerous studies indicates that in the Figure 5 Comparison of the intensity of immunoreactivity (measured as average optical density ± SEM) for PSA and PSMA according to groups: normal prostate (NP), benign prostatic hyperplasia (BPH) and prostatic carcinoma (PC) among (PSA+, PSMA+) profile. Values denoted by different superscripts are significantly different from each other. Those values sharing the same superscript are not statistically different from each other. Statistical analysis refers to each antibody separately. Significance was determined at p≤0. 05. secretory epithelial cells of prostate gland, both PSMA and PSA transcriptions are androgen-dependent [39,40]. The emergence of androgen-insensitive tumor cells aris- ing as a consequence of an adaptation to androgen with- drawal or from pre-existing androgen-independent clone [33]. According to the androgen levels, PSMA and PSA are different in several ways. In a previous report Den- meade SR et al, have identified PSMA as a gene that was up-regulated in the more aggressive androgen inde- pendent 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 1a, 25-dihy- droxyvitamin 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 expres- sion of tissue PSA has been associated to advanced prostate cancer and to transition into hormone refrac- tory tumor growth [32,20]. In addition, several experi- mental studies have shown that androgen-independent tumors are more angiogenic than androgen-dependent tumors [43]. Therefore, our finding suggests a possible cross talk between PSMA, PSA and intratumoral angio- genesis and its involvement in tumor growth and metas- tasis. This relation allowed us to classify the prostate specimens into groups according to the intensity of immunoreactions to CD34. In BPH patients, no differ- ences 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 vas- cularisation, it was found an inverse relation between angiogenesis and PSA. Unlike PSA, the highest intratu- moral 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 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. Contrary to PSMA, the results of an in vitro investigation revealed that PSA, similar to angiostatin, are implicated in suppressing angiogenesis and, therefore, also prostate cancer development or