Epidermal growth factor-induced epithelio-mesenchymal transition in human breast carcinoma cells
Epidermal growth factor-induced epithelio-mesenchymal transition in human breast carcinoma cells
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DOI：
10.1097/01.lab.0000059927.97515.fd
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发表时间：
2003-03-01
影响因子：
5
通讯作者：
Thompson, EW
中科院分区：
文献类型：
--
作者：
Ackland, ML;Newgreen, DF;Thompson, EW
PMC42-LA细胞呈现上皮表型：细胞聚集成路面上皮片，其中E-钙粘附素和β-连环素定位于细胞-细胞边界。它们大量表达细胞角蛋白，但也有5%至10%的细胞表达间充质标志物波形蛋白。在表皮生长因子(EGF)刺激下，PMC42-LA细胞发生上皮间充质转化样改变，包括波形蛋白表达上调，E-钙粘蛋白表达下调。波形蛋白在几乎所有细胞中都有表达，用EGF受体拮抗剂处理细胞后，这种增加被取消。间充质相关的细胞外基质分子纤维连接蛋白和硫酸软骨素蛋白多糖的表达也在EGF存在时增加。PMC42-LA细胞对1号胶原、IV型胶原和层粘连蛋白底物的黏附速度较快，而对纤维连接蛋白和玻璃体连接蛋白的黏附速度明显较慢。EGF提高了细胞与大多数细胞外基质分子的黏附速度，而不改变黏附偏好的顺序。EGF还引起PMC42-LA细胞运动能力的时间依赖性增加，与Vimentin染色的程度相称。运动能力的增加至少部分是化学动力学的，因为无论有没有化学吸引刺激，这都是明显的。尽管E-钙粘附素在细胞-细胞交界处的染色消失，但β-连环素仍保留在细胞外围。进一步的分析表明，N-钙粘附素存在于未处理细胞的细胞-细胞连接处，并且在EGF处理后其表达增加。N-钙粘附素和E-钙粘附素在人类癌细胞系中通常不共表达，但在胚胎组织中可以共表达，这可能意味着上皮细胞群体倾向于上皮间充质样反应。
PMC42-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 1, 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.