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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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. [4, 1] ; Macedo, Carolina C. S. [4, 1] ; Della Coletta, Ricardo [4] ; Graner, Edgard [4] ; Paes Leme, Adriana Franco [1]
Total Authors: 13
[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
Total Affiliations: 4
Document type: Journal article
Source: Molecular Cancer; v. 13, FEB 5 2014.
Web of Science Citations: 11

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)

FAPESP's process: 09/54067-3 - Acquisition of a mass spectrometer coupled to a liquid chromatography system for increasing the capacity to meet the needs of users and for making new technologies available in the Laboratory of Mass Spectrometry
Grantee:Adriana Franco Paes Leme
Support type: Multi-user Equipment Program
FAPESP's process: 10/15675-5 - Effects of modulation of the membrane metalloproteinase ADAM-17 in the extracelular subproteome using oral cancer as a model
Grantee:Fernando Moreira Simabuco
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 10/19278-0 - Study of regulation of ADAMs in oral cancer
Grantee:Adriana Franco Paes Leme
Support type: Research Grants - Young Investigators Grants