The EGF signaling pathway influences cell migration and the secretion of metalloproteinases by myoepithelial cells in pleomorphic adenoma

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• 作者：Natalia Festugatto Navarini ; Vera Cavalcanti de Araújo ; Amy Louise Brown…
• 关键词：Tumor microenvironment ; Myoepithelial cell ; Epidermal growth factor
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：36
• 期：1
• 页码：205-211
• 全文大小：547 KB
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  17. Nagase H, Visse R, Murp
• 作者单位：Natalia Festugatto Navarini (1)
  Vera Cavalcanti de Araújo (1)
  Amy Louise Brown (1)
  Fabrício Passador-Santos (1)
  Isabela Fernandes de Souza (1)
  Marcelo Henrique Napimoga (1)
  Ney Soares Araújo (1)
  Elizabeth Ferreira Martinez (1)
  
  1. Department of Oral Pathology, S?o Leopoldo Mandic Institute and Research Center, Rua José Rocha Junqueira, 13, 13045-610, Campinas, S?o Paulo, Brazil
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

During tumor development, benign neoplastic cells are influenced by the expression of cytokines, growth factors, and proteases present in the tumor microenvironment. Epidermal growth factor (EGF) is the most studied growth factor and is considered important for cell proliferation and migration. Metalloproteinases (MMPs) are also involved in tumor progression. The present study aimed to analyze the proliferation, viability and migration index of pleomorphic adenoma myoepithelial cells, in addition to the secretion of MMPs with EGF supplementation. Benign myoepithelial cells were cultured with two different EGF doses (5 and 10?ng/ml), and the influence of EGF on cell proliferation and viability, using trypan blue and MTT assays, respectively, after 24, 48, and 72?h, was evaluated. To analyze cellular morphology, hematoxylin-eosin staining and indirect immunofluorescence using the anti-vimentin antibody, was performed. In vitro migration assays were performed in Transwell chambers with an 8-μm pore covered with Matrigel and supplemented with 5 or 10?ng/ml of EGF, after 96?h. After 4?days of cell culture, ELISA was performed to determine the MMP-2 and MMP-13 levels. One-way analysis of variance (ANOVA) with post hoc Tukey test was applied, with a significance level of 0.05. The results revealed that EGF influences myoepithelial cell morphology, without alteration of proliferation and viability. The migration assay showed that EGF increased the mean index from 16?% in the control group to 40 and 76?% for 5 and 10?ng/ml of EGF, respectively. ELISA revealed that when the cells were supplemented with either?of the EGF doses, an increase in MMP-2 levels was observed when compared with the control group (C). This study concludes that EGF aids in the production of MMP-2, which favors the dissolution of the basement membrane, contributing to cell migration and tumor progression, hence permitting contact between the myoepithelial cells and stroma.