Epidermal Growth Factor-Induced Epithelio-Mesenchymal Transition in Human Breast Carcinoma Cells

Abstract

SUMMARY: PMC42-LA cells display an epithelial phenotype: the cells congregate into pavement epithelial sheets in which E-cadherin and ␤-catenin are localized at cell-cell borders. They abundantly express cytokeratins, although 5% to 10% of the cells also express the mesenchymal marker vimentin. Stimulation of PMC42-LA cells with epidermal growth factor (EGF) leads to epithelio-mesenchymal transition-like changes including up-regulation of vimentin and down-regulation of E-cadherin. Vimentin expression is seen in virtually all cells, and this increase is abrogated by treatment of cells with an EGF receptor antagonist. The expression of the mesenchyme-associated extracellular matrix molecules fibronectin and chondroitin sulfate proteoglycan also increase in the presence of EGF. PMC42-LA cells adhere rapidly to collagen I, collagen IV, and laminin-1 substrates and markedly more slowly to fibronectin and vitronectin. EGF increases the speed of cell adhesion to most of these extracellular matrix molecules without altering the order of adhesive preference. EGF also caused a time-dependent increase in the motility of PMC42-LA cells, commensurate with the degree of vimentin staining. The increase in motility was at least partly chemokinetic, because it was evident both with and without chemoattractive stimuli. Although E-cadherin staining at cell-cell junctions disappeared in response to EGF, ␤-catenin persisted at the cell periphery. Further analysis revealed that N-cadherin was present at the cell-cell junctions of untreated cells and that expression was increased after EGF treatment. N-and E-cadherin are not usually coexpressed in human carcinoma cell lines but can be coexpressed in embryonic tissues, and this may signify an epithelial cell population prone to epithelio-mesenchymal-like responses. (Lab Invest 2003, 83:435-448).

Characterization of newly established oral cancer cell lines derived from six squamous cell carcinoma and two mucoepidermoid carcinoma cells

“…Expression of the cell-cell adhesion molecule Ecadherin correlates with epithelial differentiation and and loss of E-cadherin may induce invasive growth of cancer cells (Batlle et al, 2000;Ackland et al, 2003). Our results showed that all YD cell line expressed E-cadherin.…”

Luteinising hormone-releasing hormone analogue reverses the cell adhesion profile of EGFR overexpressing DU-145 human prostate carcinoma subline

“…Presumably, such a reduction in the levels of adhesion molecules plays a major role in prostate cancer progression (Wells, 2000). How EGFR signalling limits cadherin-mediated adhesions is still being deciphered (Ackland et al, 2003;Cozzolino et al, 2003).…”

Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression

“…These cytokeratins are present in the relatively well-differentiated breast cancer lines including MCF-7 line but absent in the mesenchymal MDA-MB-231 line. PMC42-LA is heterogeneous with respect to some markers including vimentin, which suggests some plasticity with respect to phenotype (Ackland et al, 2003a).…”

“…A significant feature of PMC42-LA cells is that exposure of cells to EGF induces an EMT (Ackland et al, 2003a), including downregulation of E-cadherin and increased motility. This is typical of other systems in which EMT has been induced, such as the rat bladder cancer cell line NBT-II and the mouse mammary ScP-2 cell lines, and is also consistent with the lack of E-cadherin seen in a range of human breast carcinoma cell lines that showed in vitro invasiveness Nieman et al, 1999), as discussed above.…”