Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2018-03-21T11:50:05Z No. of bitstreams: 1 AndreiaFerreiraDoCarmo_TESE.pdf: 2170675 bytes, checksum: 49a8001d1651a77b1ebea9cb5d0cc766 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-03-23T11:55:44Z (GMT) No. of bitstreams: 1 AndreiaFerreiraDoCarmo_TESE.pdf: 2170675 bytes, checksum: 49a8001d1651a77b1ebea9cb5d0cc766 (MD5) / Made available in DSpace on 2018-03-23T11:55:44Z (GMT). No. of bitstreams: 1 AndreiaFerreiraDoCarmo_TESE.pdf: 2170675 bytes, checksum: 49a8001d1651a77b1ebea9cb5d0cc766 (MD5) Previous issue date: 2017-12-15 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O horm?nio glicoproteico estaniocalcina 2 (STC2) est? envolvido na carcinog?nese e progress?o de muitos tipos de c?ncer. No entanto, seu significado cl?nico e mecanismos moleculares no carcinoma de c?lulas escamosas oral (CCEO) foram pouco estudados e permanecem incertos. O presente estudo investigou associa??es da express?o da STC2 com par?metros clinicopatol?gicos e de sobrevida em pacientes com CCEO. Al?m disso, foram avaliados os efeitos biol?gicos causados pela redu??o dos n?veis de STC2 em linhagens celulares de CCEO e fibroblastos associados ao c?ncer (do ingl?s CAF ? carcinoma associated fibroblasts). A an?lise imunoistoqu?mica em 100 casos de CCEOs prim?rios indicou que a superexpress?o da STC2 foi associada com o par?metro N do sistema TNM e foi um fator de risco independente para sobrevida espec?fica da doen?a e sobrevida livre de doen?a em pacientes com CCEO. Usando ensaios in vitro, foi demonstrado que o silenciamento da STC2 em linhagens de CCEO promoveu a apoptose e reduziu a prolifera??o celular, migra??o, invas?o e transi??o epit?lio-mesenquimal. An?lises adicionais revelaram que o CAF expressa maiores n?veis de STC2 do que as c?lulas de CCEO. O silenciamento da STC2 no CAF reduziu a invas?o celular do CCEO, sugerindo que a STC2 liberada por CAFs contribui para um fen?tipo mais invasivo no CCEO. Esses resultados sugerem que a STC2 modula eventos importantes para a tumorig?nese oral e pode ser um biomarcador progn?stico para pacientes com CCEO. / The glycoprotein hormone stanniocalcin 2 (STC2) is involved in carcinogenesis and progression of several cancer types. However, its clinical significance and molecular mechanisms in oral squamous cell carcinoma (OSCC) have been partially studied and remain uncertain. In the present study, we investigated associations of STC2 expression with clinicopathological and survival parameters of OSCCs patients. We also determined the biological effects caused by STC2 downregulation in OSCC and cancer associated fibroblasts (CAF) cell lines. Immunohistochemical analysis in 100 cases of primary OSCC indicated that STC2 overexpression was associated with N stage (TNM staging) and was an independent risk factor for disease-specific survival and disease-free survival in patients with OSCC. Using in vitro assays, we demonstrated that STC2 knockdown in OSCC cell lines promoted apoptosis, and reduced cell proliferation, migration, invasion and epithelial-mesenchymal transition. Further analysis revealed that CAF expresses higher levels of STC2 than OSCC cells. Knockdown of STC2 in CAF reduced OSCC cell invasion, suggesting that STC2 released by CAF contributes to a more invasive phenotype in OSCC. These results suggest that STC2 modulates important events for oral tumorigenesis and can be a prognostic biomarker for OSCC.