ADAM17 mediates OSCC development in an orthotopic murine model

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Simabuco, Fernando Moreira ^{[1, 2]} ; Kawahara, Rebeca ^[1] ; Yokoo, Sami ^[1] ; Granato, Daniela C. ^[1] ; Miguel, Lucas ^[1] ; Agostini, Michelle ^[3] ; Aragao, Annelize Z. B. ^[1] ; Domingues, Romenia R. ^[1] ; Flores, Isadora L. ^{[1, 4]} ; Macedo, Carolina C. S. ^{[1, 4]} ; Della Coletta, Ricardo ^[4] ; Graner, Edgard ^[4] ; Paes Leme, Adriana Franco ^[1]

Afiliação do(s) autor(es)

^[1] CNPEM, LNBio, Lab Nacl Biociencias, Lab Espectrometria Massas, BR-13083970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Fac Ciencias Aplicadas, Limeira - Brazil

^[3] Univ Fed Rio de Janeiro, Fac Odontol, UFRJ, Rio De Janeiro - Brazil

^[4] Univ Estadual Campinas, UNICAMP, Fac Odontol Piracicaba, Piracicaba - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Cancer; v. 13, FEB 5 2014.
• Citações Web of Science: 9

Resumo

Background: ADAM17 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. Method: In 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. Results: The 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. Conclusion: These 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. (AU)

• Processo FAPESP: 09/54067-3 - EMU: aquisição de um espectrômetro de massas acoplado a cromatografia líquida para permitir ampliar a capacidade de atendimento de usuários e disponibilizar novas tecnologias no Laboratório de Espectrometria de Massas do Centro de Biologia Molecular Estrutural (ABTLUS)
• Beneficiário: Adriana Franco Paes Leme
• Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 10/15675-5 - Efeito da modulação da metaloproteinase de membrana ADAM-17 no subproteoma extracelular utilizando modelo de câncer oral
• Beneficiário: Fernando Moreira Simabuco
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 10/19278-0 - Estudo da regulação de ADAMs em câncer oral
• Beneficiário: Adriana Franco Paes Leme
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores