Calpain system protein expression and activity in ovarian cancer
Zhang, Siwei; Deen, Suha; Storr, Sarah J.; Chondrou, Panagiota S.; Nicholls, Holly; Yao, Anqi; Rungsakaolert, Ployphailin; Martin, Stewart G.
SARAH STORR firstname.lastname@example.org
Nottingham Research Fellow
Panagiota S. Chondrou
Anqi Yao ANQI.YAO@nottingham.ac.uk
STEWART MARTIN STEWART.MARTIN@NOTTINGHAM.AC.UK
Professor of Cancer and Radiation Biology
Purpose: Expression of members of the calpain system are associated with clinical outcome of patients with, amongst others, breast and ovarian cancer, 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.
Methods: 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 5 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.
Results: 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) (χ2=11.310, d.f.=1, P=0.001). Calpains 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.
Conclusions: 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.
|Journal Article Type||Article|
|Publication Date||Feb 8, 2019|
|Journal||Journal of Cancer Research and Clinical Oncology|
|Peer Reviewed||Peer Reviewed|
|APA6 Citation||Zhang, S., Deen, S., Storr, S. J., Chondrou, P. S., Nicholls, H., Yao, A., …Martin, S. G. (2019). Calpain system protein expression and activity in ovarian cancer. Journal of Cancer Research and Clinical Oncology, 145(2), 345-361. https://doi.org/10.1007/s00432-018-2794-2|
|Keywords||Calpain; Calpastatin; Ovarian cancer; Chemotherapy; Epithelial-mesenchymal transition|
Calpain system protein expression
OA (CC-BY) KJB 15.11.2018
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