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

Abstract

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.

Homoharringtonine suppresses tumor proliferation and migration by regulating EphB4-mediated β-catenin loss in hepatocellular carcinoma

“…There is a wide acceptance that EMT is a prerequisite for cell migration and β-catenin can trigger EMT 23 , 29 , yet whether EphB4 could regulate β-catenin remains unknown. β-catenin was the key molecule of the Wnt/β-catenin pathway and the nuclear translocation of which could not only promote the expression of matrix metalloproteinases (MMPs) but also suppress E-cadherin expression 30 , 31 . In this study, both TCGA database and our own HCC patient samples analysis demonstrated that β-catenin was significantly overexpressed in HCC patients at protein and mRNA levels.…”

EGF and a GSK3 Inhibitor Deplete Junctional E-cadherin and Stimulate Proliferation in the Mature Mammalian Ear

“…EGF also has been shown to induce E-cadherin internalization via caveolin-mediated endocytosis (Lu et al, 2003), micropinocytosis (Bryant et al, 2007), and following Hakai-mediated ubiquitination via Src (Shen et al, 2008). EGF also can also induce proteolytic cleavage of E-cadherin by matrix metalloproteases (Cowden Dahl et al, 2008;Zheng et al, 2009;Chavez et al, 2012;Navarini et al, 2017). Additional studies will be required to determine which of those potential mechanisms may be responsible for the depletion of E-cadherin that occurs in striolar SCs exposed to EGF and CHIR-99021.…”

The Cross-Talk Between EGFR and E-Cadherin

“…Finally, EGFR activation may further inhibit E-cadherin-mediated adhesion through proteolytic cleavage of E-cadherin. The secretion of matrix metalloproteinase-2 (MMP-2) is enhanced by EGF supplementation in salivary gland pleomorphic adenoma cells ( Navarini et al, 2017 ), whereas in some ovarian cancer cell lines (OVEA6 and OVCA 429 but not DOV13 and OVCA 432) EGFR activation increases the expression of matrix metalloproteinase-9 (MMP-9) ( Ellerbroek et al, 1998 ). Conversely, EGF produced by lymphoma cells inhibits MMP-9 expression in neighbouring stromal cells through induction of Egr-1 expression ( Bouchard et al, 2010 ).…”