Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior
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Luciana Bueno Ferreira1,2, Catarina Tavares1,2, Ana Pestana1,2, Catarina Leite Pereira1,5,6, Catarina Eloy2, Marta Teixeira Pinto1,2, Patricia Castro1,2,4, Rui Batista1,2, Elisabete Rios1,2,3,4, Manuel Sobrinho-Simões1,2,3,4, Etel Rodrigues Pereira Gimba7,8, Paula Soares1,2,3
1Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
2Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) – Cancer Signalling and Metabolism, 4200-465 Porto, Portugal
3Medical Faculty, University of Porto, P-4200 Porto, Portugal
4Department of Pathology, Hospital de S. João, P-4200 Porto, Portugal
5INEB – Instituto de Engenharia Biomédica, 4200-135 Porto, Portugal
6ICBAS – Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto, 4050-313 Porto, Portugal
7Research Coordination, National Institute of Cancer, Rio de Janeiro 22743-051, Brazil
8Natural Sciences Department, Health and Humanities Institute, Fluminense Federal University, Rio de Janeiro 28895-532, Brazil
Paula Soares, email: [email protected]
Etel Rodrigues Pereira Gimba, email: [email protected]
Keywords: osteopontin splice variants (OPN-SV), osteopontin-a (OPNa), thyroid cancer, migration, invasion
Received: May 06, 2016 Accepted: June 18, 2016 Published: July 07, 2016
Osteopontin (OPN) is a matricellular protein overexpressed in cancer cells and modulates tumorigenesis and metastasis, including in thyroid cancer (TC). The contribution of each OPN splice variant (OPN-SV), named OPNa, OPNb and OPNc, in TC is currently unknown. This study evaluates the expression of total OPN (tOPN) and OPN-SV in TC tissues and cell lines, their correlation with clinicopathological, molecular features and their functional roles. We showed that tOPN and OPNa are overexpressed in classic papillary thyroid carcinoma (cPTC) in relation to adjacent thyroid, adenoma and follicular variant of papillary thyroid carcinoma (fvPTC) tissues. In cPTC, OPNa overexpression is associated with larger tumor size, vascular invasion, extrathyroid extension and BRAFV600E mutation. We found that TC cell lines overexpressing OPNa exhibited increased proliferation, migration, motility and in vivo invasion. Conditioned medium secreted from cells overexpressing OPNa induce MMP2 and MMP9 metalloproteinases activity. In summary, we described the expression pattern of OPN-SV in cPTC samples and the key role of OPNa expression on activating TC tumor progression features. Our findings highlight OPNa variant as TC biomarker, besides being a putative target for cPTC therapeutic approaches.
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