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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

EGFR signaling downstream of EGF regulates migration, invasion, and MMP secretion of immortalized cells derived from human ameloblastoma

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Autor(es):
Pinheiro da Rosa, Marina Rolo [1] ; Carreira Falcao, Aline Semblano [1] ; Fuzii, Hellen Thais [2] ; da Silva Kataoka, Maria Sueli [1] ; Ribeiro, Andre L. R. [1, 3] ; Boccardo, Enrique [4] ; de Siqueira, Adriane Sousa [5] ; Jaeger, Ruy G. [5] ; Viana Pinheiro, Joao de Jesus [1] ; Alves Junior, Sergio de Melo [1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Fed Univ Para UFPA, Sch Dent, Dept Oral & Maxillofacial Pathol, Belem, Para - Brazil
[2] Fed Univ Para UFPA, Inst Trop Med, Belem, Para - Brazil
[3] Univ Ctr Para CESUPA, Sch Dent, Dept Oral & Maxillofacial Surg, Belem, Para - Brazil
[4] Univ Sao Paulo, Dept Microbiol, Inst Biomed Sci, Sao Paulo - Brazil
[5] Univ Sao Paulo, Dept Cell & Dev Biol, Inst Biomed Sci, Sao Paulo - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: TUMOR BIOLOGY; v. 35, n. 11, p. 11107-11120, NOV 2014.
Citações Web of Science: 19
Resumo

Ameloblastoma is an odontogenic tumor characterized by local invasiveness and frequent recurrence. The surrounding stroma, composed of different cell types and extracellular matrix (ECM), may influence ameloblastoma invasive behavior. Furthermore, tumor and stromal cells secrete matrix metalloproteases (MMPs), which, in turn, can modulate the matrix and promote the release of ECM-bound growth factors. Among these growth factors, epidermal growth factor (EGF) and its receptor, EGFR, have already been shown to stimulate MMP synthesis, suggesting that an interdependent mechanism, involving MMP activity and growth factors release, may contribute to tumor invasiveness. The aim of this study was to evaluate the effects of the EGF/EGFR signaling pathway on migration, invasion, and MMP activity, in a primary cell line derived from human ameloblastoma. We established and characterized a primary cell line (AME-1) from a human ameloblastoma sample. This cell line was transduced with human papillomavirus type 16 (HPV16) E6/E7 oncogenes, generating the AME-HPV continuous cell line. EGF, MMP2, and MMP9 expression in ameloblastoma biopsies and in the AME-HPV cell line was analyzed by immunohistochemistry and immunofluorescence, respectively. Migratory activity of EGF-treated AME-HPV cells was investigated using monolayer wound assays and Transwell chambers. EGF-induced invasion was assessed in Boyden chambers coated with Matrigel. Conditioned medium from EGF-treated cells was subjected to zymography. EGFR expression in AME-HPV cells was silenced by small interfering RNA (siRNA), to verify the relationship between this receptor and MMP secretion. Ameloblastoma samples and AME-HPV cells expressed EGF, EGFR, MMP2, and MMP9. AME-HPV cells treated with EGF showed increased rates of migration and invasion, as well as enhanced MMP2 and MMP9 activity. EGFR knockdown decreased MMP2 and MMP9 levels in AME-HPV cells. EGFR signaling downstream of EGF probably regulates migration, invasion, and MMP secretion of ameloblastoma-derived cells. (AU)

Processo FAPESP: 09/17336-6 - Peptídeos bioativos da laminina induzindo invadopódios em linhagem celular derivada de carcinoma epidermóide: estudo dinâmico por microscopia 4D
Beneficiário:Adriane Sousa de Siqueira
Modalidade de apoio: Bolsas no Brasil - Doutorado