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Epidermal growth factor-induced epithelio-mesenchymal transition in human breast carcinoma cells
journal contribution
posted on 2003-03-01, 00:00 authored by Leigh AcklandLeigh Ackland, D Newgreen, M Fridman, M Waltham, A Arvanitis, J Minichiello, J Price, E ThompsonPMC42-LA cells display an epithelial phenotype: the cells congregate into pavement epithelial sheets in which E-cadherin and beta-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, beta-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.
History
Journal
Laboratory investigationVolume
83Issue
3Pagination
435 - 448Publisher
United States and Canadian Academy of PathologyLocation
Baltimore, Md.ISSN
0023-6837eISSN
1530-0307Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2003, United States and Canadian Academy of PathologyUsage metrics
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Science & TechnologyLife Sciences & BiomedicineMedicine, Research & ExperimentalPathologyResearch & Experimental MedicineTRANSCRIPTION FACTOR SNAILEMBRYONIC NEURAL CELLSE-CADHERIN EXPRESSIONCANCER CELLSEPITHELIOMESENCHYMAL TRANSFORMATIONLINE PMC42VIMENTIN EXPRESSIONGENE-EXPRESSIONN-CADHERININTERMEDIATE FILAMENTS
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