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Ben Jemaa A.,University of Carthage | Sallami S.,Hospital of la Rabta Tunis | Ramarli D.,Giovanni Battista Rossi Hospital | Colombatti M.,Giovanni Battista Rossi Hospital | Oueslati R.,University of Carthage
Inflammation | Year: 2013

The aim of the present work was to study the expression of the proinflammatory cytokine, interleukin-6 (IL-6), mediated by bFGF signaling and its possible crosstalk with prostate-specific membrane antigen (PSMA) in LNCaP and PC3-PSMA prostate cancer cell lines. PC3 cells stably transfected with PSMA gene were used for restoring PSMA expression. LNCaP and PC3-PSMA cells were exposed to 10 ng/mL of basic fibroblast growth factor (bFGF). IL-6 production was measured by ELISA assay, and levels of PSMA expression were assessed by flow cytometry. AKT, ERK1/2, and p38 phosphorylation were detected by Western blot. bFGF enhances IL-6 production in LNCaP and PC3-PSMA prostate cancer cells. The effect of bFGF on stimulating IL-6 secretion was greater in LNCaP than in PC3-PSMA cells. In the presence of bFGF, PSMA expression was activated after 4 days of treatment in LNCaP and PC3-PSMA cells. This activation was not maintained after long term of treatment in both metastatic cell lines. Solely MAPKs pathways (ERK1/2 and p38) were activated after bFGF stimulation in both metastatic cell lines, whereas AKT did not show any activation. The interference of the proinflammatory cytokine, IL-6, with bFGF signaling and PSMA, should be of high clinical relevance in the treatment of metastatic prostate cancer. In developing novel therapeutic modalities targeting IL-6, significant attention should be given to PSMA and its inactivation to fight against prostate cancer. © 2012 Springer Science+Business Media New York.


Ben Jemaa A.,University of Carthage | Bouraoui Y.,University of Carthage | Sallami S.,Hospital of la Rabta Tunis | Banasr A.,Hospital of Charles Nicolle Tunis | And 5 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2010

Background. The present study was undertaken to relate the co-expression of prostate-associated antigens, PSMA and PSA, with the degree of vascularization in normal and pathologic (hyperplasia and cancer) prostate tissues to elucidate their possible role in tumor progression. Methods. The study was carried out in 6 normal, 44 benign prostatic hyperplastic and 39 cancerous human prostates. Immunohistochemical analysis were performed using the monoclonal antibody CD34 to determine the angiogenic activity, and the monoclonal antibodies 3E6 and ER-PR8 to assess PSMA and PSA expression, respectively. Results. In our study we found that in normal prostate tissue, PSMA and PSA were equally expressed (3.7 0.18 and 3.07 0.11). A significant difference in their expression was see in hyperplastic and neoplastic prostates tissues (16.14 0.17 and 30.72 0.85, respectively) for PSMA and (34.39 0.53 and 17.85 1.21, respectively) for PSA. Study of prostate tumor profiles showed that the profile (PSA+, PSMA-) expression levels decreased between normal prostate, benign prostatic tissue and primary prostate cancer. In the other hand, the profile (PSA-, PSMA+) expression levels increased from normal to prostate tumor tissues. PSMA overexpression was associated with high intratumoral angiogenesis activity. By contrast, high PSA expression was associated with low angiogenesis activity. Conclusion. These data suggest that these markers are regulated differentially and the difference in their expression showed a correlation with malignant transformation. With regard to the duality PSMA-PSA, this implies the significance of their investigation together in normal and pathologic prostate tissues. © 2010 Ben Jemaa et al; licensee BioMed Central Ltd.


Jemaa A.B.,University of Carthage | Bouraoui Y.,University of Carthage | Rais N.B.,Hospital of Military Tunis | Nouira Y.,Hospital of La Rabta Tunis | Oueslati R.,University of Carthage
Immunobiology | Year: 2016

Background: Several PSMA-PSA prostate clones have been identified during prostate cancer progression; however, until now, their . in situ inflammatory characteristics have remained unclear. Aim: We therefore investigated the interplay between proinflammatory cytokines and (PSMA,PSA) sub-groups. Materials and methods: 27 benign prostate hyperplasia (BPH) and 18 prostate cancers (PC) were enrolled in this study. Immunohistochemical analysis was performed. Serum levels of PSA were assayed by Immulite autoanalyser. Results: In BPH and PC patients with elevated serum PSA levels, IL-1α was the most proinflammatory cytokine expressed in (PSMA+,PSA-) subgroup. However, most samples of (PSMA+,PSA+) subgroup had positive immunoreaction to IL-6. In samples of PC with PSA serum levels of 4-20. ng/mL or >20. ng/mL, immunoreaction to TNF-α was seen only in (PSMA+,PSA+) subgroup. Interestingly, several combinations of proinflammatory cytokines (IL-6, IL-1α and TNF-α) showed that coexpression of tissue PSMA and PSA was concomitant with high immunoreactions to (IL-6+,TNF-α-), (IL-6+,IL-1α+) and (IL-1α+,TNFα-) in BPH and PC patients. (PSMA,PSA) subgroup lacking tissue PSA expression showed a high immunoexpression of the profile (IL-6+,TNF-α-). The combinations of (IL-6-, TNF-α-) and (IL-6-, IL-1α-) were absent in (PSMA+,PSA-) and (PSMA+,PSA+) BPH sub-groups. Conclusion: Collectively, these findings underscore the importance of TNF-α and highlight the interaction between IL-6 and IL-1α to generate an inflammatory microenvironment in driving (PSMA,PSA) prostate clones. © 2016 Elsevier GmbH.


Jemaa A.B.,University of Carthage | Bouraoui Y.,University of Carthage | Sallami S.,Hospital of la Rabta Tunis | Banasr A.,Hospital of Charles Nicolle Tunis | And 2 more authors.
Journal of Immunoassay and Immunochemistry | Year: 2014

Prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) measured in serum are not fully satisfactory as biomarkers of prostate cancer (PC). Results obtained in this article indicated that PSMA/PSA ratio evaluated by immunohistochemistry in normal prostate (NP), benign prostatic hyperplasia (BPH), and PC at the individual level could be a useful tool for diagnosis and prognosis of PC. PSMA and PSA were equally expressed in NP and the PSMA/PSA ratio was 1.22 ± 0.15. Data also indicated that PSMA/PSA ratio fluctuates in BPH and PC compared to NP. In BPH, the PSMA/PSA ratio was around 0.47 ± 0.02, whereas it's significantly increased in PC, about 4.95 ± 0.83. In parallel, the highest PSMA/PSA ratio was associated with high intratumoral angiogenesis in PC patients with (PSMA+,PSA+) profile. © 2014 Taylor and Francis Group, LLC.


Ben Jemaa A.,University of Carthage | Bouraoui Y.,University of Carthage | Sallami S.,Hospital of La Rabta Tunis | Banasr A.,Hospital of Charles Nicolle Tunis | And 2 more authors.
Journal of Biological Research (Greece) | Year: 2013

In this study we investigate differences in the biological features between two most abundant pro state tumor profiles (PSMA+, PSA+) and (PSMA+, PSA-) in benign prostatic hyperplasia (BPH) and prostate cancer (PC) tissues according to the activation of AKT (T308/S473) and angi ogenic activity. This study was carried out in 6 normal prostates (NP), 25 BPH, and 23 PC tissues with dominant Gleason grade ≥8. Prostate tissues were stained using immunohistochemistry me thod with anti-PSMA, anti-PSA, anti-p-AKT (T308), anti-p-AKT (S473) or anti-CD34 antibodies. Our results showed that among the (PSMA+, PSA+) and (PSMA+, PSA-) profiles in these tis sues, the highest optical densities for p-AKT (T308) and p-AKT (S473) were found in PC speci mens. Interestingly, in PC patients, the intensities of immunoreactions to p-AKT (T308) and p-AKT (S473) decreased significantly from (PSMA+, PSA+) to (PSMA+, PSA-) profiles. Similar to p-AKT (T308) and p-AKT (S473), PSMA immunoreaction and angiogenic activity declined significantly from (PSMA+, PSA+) to (PSMA+, PSA-) profiles in PC tissues. Despite being dis tinguishable prostate tumor profiles, (PSMA+, PSA+) and (PSMA+, PSA-) exhibited similar bio logical features in BPH patients for AKT activation (T308/S473) and angiogenic activity. How ever, PC patients with (PSMA+, PSA+) profile exhibited a feature of invasive potential and more aggressive phenotype than those with (PSMA+, PSA-) profile. Distinguishing PC subtypes based on PSMA-PSA profiles may improve stratifying disease outcome and treatment response.

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