Journal
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 145, Issue 2, Pages 345-361Publisher
SPRINGER
DOI: 10.1007/s00432-018-2794-2
Keywords
Calpain; Calpastatin; Ovarian cancer; Chemotherapy; Epithelial-mesenchymal transition
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PurposeExpression 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.MethodsCalpain-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 RT2 Profiler PCR Array.ResultsThe 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) ((2)=11.310, df=1, P=0.001). Calpain and calpastatin expression varied among ovarian cancer cell lines yet their expression levels were similar between chemo-sensitive cells and resistant counterparts. Moreover, calpeptin treatment did not alter cellular response to platinum-based chemotherapy or epithelial-mesenchymal transition-related gene expression.ConclusionsThe 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.
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