Literature DB >> 18311384

The role of TGF-beta-1 protein and TGF-beta-R-1 receptor in immune escape mechanism in bladder cancer.

Amira Helmy1, Olfat Ali Hammam, Tarek Ramzy El Lithy, Mohamed Mohi El Deen Wishahi.   

Abstract

BACKGROUND: Tumor cells have numerous immune surveillance escape mechanisms as well as means of resistance to apoptosis. This study tried to clarify one of these mechanisms in bladder cancer with the hope of being able to develop targeted therapy that will sensitize the tumor cells to immune-mediated apoptosis.
METHODS: In this study, electron microscopic examination and expression of TGF-beta-1 protein and TGF-beta-R-1 receptor using immunoelectronmicroscopic and immunocytochemical techniques were investigated in urine and peripheral blood mononuclear cells (PBMNCs). Samples were obtained from 5 healthy controls (Group 1) and 60 study patients who were classified according to the cytopathologic examination of their urine into 2 main subgroups: chronic cystitis (bilharzial and nonbilharzial, Group 2, n = 15) and bladder cancer (transitional cell carcinoma and squamous cell carcinoma, Group 3, n = 45).
RESULTS: Examination of PBMNCs by immunoelectronmicroscopic and immunocytochemical techniques showed a significant increase in the percentage of positive cases expressing both TGF-beta-1 protein and TGF-beta-R-1 receptors in bladder cancer in comparison with the control (P < .01 and P < .05, respectively) and with chronic cystitis (P < .05). By electron microscopic examination, 42 out of 45 bladder cancer cases (93.3%) revealed remarkable apoptotic changes represented by cell shrinkage, surface blebs, nuclear chromatin condensation, and vacuolated cytoplasm. Urine examination by immunoelectronmicroscopic and immunocytochemical techniques revealed a statistically significant decrease in the percentage of positive cases expressing TGF-beta-R1 receptor in bladder cancer in comparison with either chronic cystitis cases or controls (P < .01), while TGF-beta-1 protein was significantly increased (P < .01). By electron microscopic examination, exfoliated necrotic malignant epithelial (urothelial) cells and many inflammatory cells were detected.
CONCLUSIONS: This work helps researchers and clinicians to better understand one of the escape mechanisms in bladder cancer that may facilitate the reverse of tumor escape from the immune system. It also draws attention to TGF-beta-1 protein and TGF-beta-R1 receptor; TGF-beta-1 protein can be used as an attractive target for anticancer therapy, and the absence of TGF-beta-R1 can be considered a marker for malignant transformation of urothelial cells in bladder cancer.

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Year:  2007        PMID: 18311384      PMCID: PMC2234299     

Source DB:  PubMed          Journal:  MedGenMed        ISSN: 1531-0132


  51 in total

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