Annexin A2 is regulated by ovarian cancer-peritoneal cell interactions and promotes metastasis
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Noor A. Lokman1, Alison SF. Elder1, Miranda P. Ween2, Carmen E. Pyragius1, Peter Hoffmann3, Martin K. Oehler1,4,* and Carmela Ricciardelli 1,*
1 Robinson Institute, Research Centre for Reproductive Health, School of Paedriatrics and Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia
2 Research Centre for Infectious Diseases, School of Molecular Biosciences, University of Adelaide, Adelaide, SA 5005, Australia
3 Adelaide Proteomics Centre, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005, Australia
4 Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, SA 5005, Australia
* The last two authors share senior authorship.
Carmela Ricciardelli, email:
Keywords: annexin A2, ovarian cancer, invasion, chick chorioallantoic membrane assay, xenograft model
Received: June 25, 2013 Accepted: July 12, 2013 Published: July 14, 2013
Our recent research identified the protein annexin A2 to be regulated by ovarian cancer-peritoneal cell interactions. This study investigated the role of annexin A2 in ovarian cancer metastasis and its potential utility as a novel therapeutic target, using in vitro and in vivo ovarian cancer models. Annexin A2 expression was examined by qRT-PCR and western blotting in ovarian cancer cell lines and immunohistochemistry in serous ovarian carcinoma tissues. Annexin A2 siRNAs were used to evaluate the effects of annexin A2 suppression on ovarian cancer cell adhesion, motility, and invasion. Furthermore, annexin A2 neutralizing antibodies were used to examine the role of annexin A2 in tumor invasion and metastasis in vivo using a chick chorioallantoic membrane assay and an intraperitoneal xenograft mouse model. Strong annexin A2 immunostaining was observed in 90% (38/42) of the serous ovarian cancer cells and was significantly increased in the cancer-associated stroma compared to non-malignant ovarian tissues. Annexin A2 siRNA significantly inhibited the motility and invasion of serous ovarian cancer cells and adhesion to the peritoneal cells. Annexin A2 neutralizing antibodies significantly inhibited OV-90 cell motility and invasion in vitro and in vivo using the chick chorioallantoic membrane assay. The growth of SKOV-3 cells and their peritoneal dissemination in nude mice was significantly inhibited by annexin A2 neutralizing antibodies. Annexin A2 plays a critical role in ovarian cancer metastasis and is therefore a potential novel therapeutic target against ovarian cancer.
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