Produção Nacional
Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior
2016; Impact Journals LLC; Volume: 7; Issue: 32 Linguagem: Inglês
10.18632/oncotarget.10468
ISSN1949-2553
AutoresLuciana Bueno Ferreira, Catarina Tavares, Ana Pestana, Catarina Leite Pereira, Catarina Eloy, Marta Pinto, Patrícia Castro, Rui Batısta, Elisabete Rios, Manuel Sobrinho‐Simões, Etel Rodrigues Pereira Gimba, Paula Soares,
Tópico(s)Oral and Maxillofacial Pathology
Resumo// Luciana Bueno Ferreira 1, 2 , Catarina Tavares 1, 2 , Ana Pestana 1, 2 , Catarina Leite Pereira 1, 5, 6 , Catarina Eloy 2 , Marta Teixeira Pinto 1, 2 , Patricia Castro 1, 2, 4 , Rui Batista 1, 2 , Elisabete Rios 1, 2, 3, 4 , Manuel Sobrinho-Simões 1, 2, 3, 4 , Etel Rodrigues Pereira Gimba 7, 8 , Paula Soares 1, 2, 3 1 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal 2 Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) – Cancer Signalling and Metabolism, 4200-465 Porto, Portugal 3 Medical Faculty, University of Porto, P-4200 Porto, Portugal 4 Department of Pathology, Hospital de S. João, P-4200 Porto, Portugal 5 INEB – Instituto de Engenharia Biomédica, 4200-135 Porto, Portugal 6 ICBAS – Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto, 4050-313 Porto, Portugal 7 Research Coordination, National Institute of Cancer, Rio de Janeiro 22743-051, Brazil 8 Natural Sciences Department, Health and Humanities Institute, Fluminense Federal University, Rio de Janeiro 28895-532, Brazil Correspondence to: Paula Soares, email: psoares@ipatimup.pt Etel Rodrigues Pereira Gimba, email: etelgimba@id.uff.br 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 BRAF V600E 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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