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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.

Authors

Siwei Zhang

Suha Deen

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SARAH STORR sarah.storr@nottingham.ac.uk
Nottingham Research Fellow

Panagiota S. Chondrou

Holly Nicholls

Anqi Yao ANQI.YAO@nottingham.ac.uk

Ployphailin Rungsakaolert

STEWART MARTIN STEWART.MARTIN@NOTTINGHAM.AC.UK
Professor of Cancer and Radiation Biology



Abstract

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
Print ISSN 0171-5216
Electronic ISSN 1432-1335
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 145
Issue 2
Pages 345-361
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
DOI https://doi.org/10.1007/s00432-018-2794-2
Keywords Calpain; Calpastatin; Ovarian cancer; Chemotherapy; Epithelial-mesenchymal transition
Publisher URL https://link.springer.com/article/10.1007%2Fs00432-018-2794-2

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Copyright Statement
OA (CC-BY) KJB 15.11.2018





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