Effect of epithelial growth factor on matrix metalloproteinase-2 and E-cadherin/β-catenin expression in an in situ model of tumorigenesis

Oncol Lett. 2017 Sep;14(3):3136-3140. doi: 10.3892/ol.2017.6513. Epub 2017 Jun 30.

Abstract

The aim of the present study was to analyze the in vitro effect of various doses of epidermal growth factor (EGF; 5 and 10 ng/ml) on matrix metalloproteinase-2 (MMP-2) secretion and E-cadherin/β-catenin expression by co-cultured cells that mimic an in situ carcinoma ex-pleomorphic adenoma, where benign myoepithelial cells from a pleomorphic adenoma surround malignant epithelial cells. EGF was supplemented in various doses and the effects were evaluated following four days of cell culture. ELISA was performed to determine MMP-2 secretion levels. Gene expression for E-cadherin and β-catenin was analyzed using quantitative polymerase chain reaction. The results revealed that E-cadherin expression decreased when the cells were supplemented with 5 ng/ml EGF. ELISA results indicated that MMP-2 secretion increased when EGF was supplemented at concentrations of 5 and 10 ng/ml. The present findings demonstrated that EGF may be involved in the epithelial-mesenchymal transition process via altering the E-cadherin/β-catenin complex and increasing MMP-2 secretion, which may then favor the dissolution of the basement membrane to the benefit of malignant cell clusters, contributing to the development of an invasive phenotype in this in vitro model of tumorigenesis.

Keywords: E-cadherin; epithelial growth factor; matrix metalloproteinase-2; myoepithelial cell; tumor microenvironment; β-catenin.