calpastatin and Endometrial-Neoplasms

Expression of members of the calpain system are associated with clinical outcome of patients with, amongst others, breast and ovarian cancers, with calpain-2 expression in ovarian cancer being implicated in chemo-resistance and survival. This study aimed, using a large patient cohort and in vitro models, to verify its importance and further investigate the role in ovarian cancer chemoresponse.. Calpain-1, calpain-2, calpain-4 and calpastatin expression were evaluated in primary ovarian carcinomas (n = 575) by immunohistochemistry. Protein expression was assessed, via western blotting, in five ovarian cancer cell lines with various sensitivities towards cisplatin/carboplatin. In vitro calpain activity was inhibited by calpeptin treatment to assess changes in platinum sensitivity by proliferation assay, with expression of genes associated with epithelial-mesenchymal transition being examined by RT. The current study confirmed previous data that high calpain-2 expression is associated with poor overall survival (P = 0.026) and that calpain-1 was not associated with overall survival or progression-free survival. Low expression of calpastatin (P = 0.010) and calpain-4 (P = 0.003) were also associated with adverse survival. Such prognostic associations do not seem to be linked with altered tumour sensitivity towards platinum-based chemotherapy. Interestingly, low calpain-1 expression was more frequent in patients with confined tumours (stage 1) (χ. The conventional calpains and calpastatin have been confirmed to play an important role in ovarian cancer; however, the precise mechanisms whereby they exert effects remain to be elucidated.

Topics: Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Calcium-Binding Proteins; Calpain; Cell Proliferation; Cohort Studies; Cystadenocarcinoma, Serous; Endometrial Neoplasms; Epithelial-Mesenchymal Transition; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Middle Aged; Ovarian Neoplasms; Prognosis; Survival Rate; Tumor Cells, Cultured

Calpains (CAPN) are intracellular, non-lysosomal cytoplasmic cysteine endopeptidases and they are expressed ubiquitously. Their endogenous specific inhibitor is calpastatin. When calcium is present, calpastatin and calpain attach to each other, inhibiting the protease. The calpain system plays an important role in many processes including apoptosis, necrosis, ischaemia and exocytosis. The role of calpains in pathogenesis or further tumour progression has been proved in related studies. This study focused on the expression of the enzymes calpain 1, calpain 2 and the inhibitor calpastatin in normal and malignant endometrial tissue.. Immunohistochemical stainings were performed on paraffin slices and staining intensity, percentage of positive cells and international ratio score were evaluated.. The endometrial carcinoma showed a higher expression of calpastatin than benign endometrial tissue.

Topics: Calcium-Binding Proteins; Calpain; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Middle Aged; Neoplasm Staging