ADAM17 mediates OSCC development in an orthotopic murine model

Molecular Cancer

Research

Edgard Graner¹  Ricardo Della Coletta¹  Michelle Agostini²  Rebeca Kawahara³  Sami Yokoo³  Romênia R Domingues³  Adriana Franco Paes Leme³  Daniela C Granato³  Annelize ZB Aragão³  Lucas Miguel³  Fernando Moreira Simabuco⁴  Carolina CS Macedo⁵  Isadora L Flores⁵ 

[1] Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, UNICAMP, Piracicaba, Brazil;Faculdade de Odontologia, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil;Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, 13083-970, Campinas, Brazil;Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, 13083-970, Campinas, Brazil;Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, UNICAMP, Limeira, Brazil;Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, 13083-970, Campinas, Brazil;Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, UNICAMP, Piracicaba, Brazil;

关键词: Epidermal Growth Factor Receptor;    Oral Cancer;    Oral Squamous Cell Carcinoma;    Oral Squamous Cell Carcinoma;    Collagenase Activity;   

DOI  :  10.1186/1476-4598-13-24

 received in 2013-09-11, accepted in 2014-02-03,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundADAM17 is one of the main sheddases of the cells and it is responsible for the cleavage and the release of ectodomains of important signaling molecules, such as EGFR ligands. Despite the known crosstalk between ADAM17 and EGFR, which has been considered a promising targeted therapy in oral squamous cell carcinoma (OSCC), the role of ADAM17 in OSCC development is not clear.MethodIn this study the effect of overexpressing ADAM17 in cell migration, viability, adhesion and proliferation was comprehensively appraised in vitro. In addition, the tumor size, tumor proliferative activity, tumor collagenase activity and MS-based proteomics of tumor tissues have been evaluated by injecting tumorigenic squamous carcinoma cells (SCC-9) overexpressing ADAM17 in immunodeficient mice.ResultsThe proteomic analysis has effectively identified a total of 2,194 proteins in control and tumor tissues. Among these, 110 proteins have been down-regulated and 90 have been up-regulated in tumor tissues. Biological network analysis has uncovered that overexpression of ADAM17 regulates Erk pathway in OSCC and further indicates proteins regulated by the overexpression of ADAM17 in the respective pathway. These results are also supported by the evidences of higher viability, migration, adhesion and proliferation in SCC-9 or A431 cells in vitro along with the increase of tumor size and proliferative activity and higher tissue collagenase activity as an outcome of ADAM17 overexpression.ConclusionThese findings contribute to understand the role of ADAM17 in oral cancer development and as a potential therapeutic target in oral cancer. In addition, our study also provides the basis for the development of novel and refined OSCC-targeting approaches.

【 授权许可】

Unknown   
© Simabuco et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.