Oncotarget

Research Papers:

Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior

Luciana Bueno Ferreira, Catarina Tavares, Ana Pestana, Catarina Leite Pereira, Catarina Eloy, Marta Teixeira Pinto, Patricia Castro, Rui Batista, Elisabete Rios, Manuel Sobrinho-Simões, Etel Rodrigues Pereira Gimba and Paula Soares _

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Oncotarget. 2016; 7:52003-52016. https://doi.org/10.18632/oncotarget.10468

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Abstract

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

Correspondence to:

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

ABSTRACT

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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