title: Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior.
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.
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer Signalling and Metabolism, 4200-465 Porto, Portugal.
authors.forename: Luciana Bueno
authors.initials: LB
authors.lastname: Ferreira
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer Signalling and Metabolism, 4200-465 Porto, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Tavares
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer Signalling and Metabolism, 4200-465 Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Pestana
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.|INEB - Instituto de Engenharia Biomédica, 4200-135 Porto, Portugal.|ICBAS - Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto, 4050-313 Porto, Portugal.
authors.forename: Catarina Leite
authors.initials: CL
authors.lastname: Pereira
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer Signalling and Metabolism, 4200-465 Porto, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Eloy
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer Signalling and Metabolism, 4200-465 Porto, Portugal.
authors.forename: Marta Teixeira
authors.initials: MT
authors.lastname: Pinto
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer Signalling and Metabolism, 4200-465 Porto, Portugal.|Department of Pathology, Hospital de S. João, P-4200 Porto, Portugal.
authors.forename: Patricia
authors.initials: P
authors.lastname: Castro
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer Signalling and Metabolism, 4200-465 Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Batista
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer Signalling and Metabolism, 4200-465 Porto, Portugal.|Medical Faculty, University of Porto, P-4200 Porto, Portugal.|Department of Pathology, Hospital de S. João, P-4200 Porto, Portugal.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Rios
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer Signalling and Metabolism, 4200-465 Porto, Portugal.|Medical Faculty, University of Porto, P-4200 Porto, Portugal.|Department of Pathology, Hospital de S. João, P-4200 Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
authors.affiliation: Research Coordination, National Institute of Cancer, Rio de Janeiro 22743-051, Brazil.|Natural Sciences Department, Health and Humanities Institute, Fluminense Federal University, Rio de Janeiro 28895-532, Brazil.
authors.forename: Etel Rodrigues Pereira
authors.initials: ER
authors.lastname: Gimba
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer Signalling and Metabolism, 4200-465 Porto, Portugal.|Medical Faculty, University of Porto, P-4200 Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
mesh_terms: D002291:Carcinoma, Papillary / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D053495:Osteopontin / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000473:pathology*
chemical_list: D020033:Protein Isoforms; C506895:SPP1 protein, human; D053495:Osteopontin
keywords: invasion; migration; osteopontin splice variants (OPN-SV); osteopontin-a (OPNa); thyroid cancer