An overview of epithelio-mesenchymal transformation.
An overview of epithelio-mesenchymal transformation.
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DOI：
10.1159/000147748
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
E. Hay
中科院分区：
文献类型：
--
作者：
E. Hay
上皮型是脊索门的早期胚胎和原始成体的组织表型。然而，第二种组织类型是由高等脊索动物(如脊椎动物)的上皮-间充质转化(EMT)产生的。间充质细胞有能力通过细胞外基质(ECM)侵袭和迁移，造成戏剧性的细胞换位，这是真正的上皮细胞所不具备的。羊膜脊椎动物的原始间充质细胞从原始纹路迁移到中胚层和内胚层上皮细胞。具有结缔组织和肌肉潜能的最终间充质来自上皮中胚层，几乎与神经脊间充质形成于外胚层的时间相同。在后来的胚胎发育过程中。EMT被用来重塑不需要的上皮细胞，如腭部内侧边缘的上皮细胞。我们讨论了上皮细胞转化为间充质细胞的机制，反之亦然。一方面，细胞激活可能的间充质主控基因，关闭上皮基因，并获得运动机制，使其能够通过肌动蛋白皮质与细胞外基质在三维(3D)中相互作用，同时将内质滑动到新的前端。另一方面，原代间充质细胞可以重新激活上皮调控基因，如E-钙粘附素，关闭侵袭ECM的运动机制，并重新表达心尖-基底极性。我们综述了在细胞向间充质转化过程中被激活的FSP1、src、ras和fos基因，以及它们的邻居激活的诱导内膜转化的基因，如转化生长因子β、NT-3和声波刺猬。在3D胶原凝胶中的悬浮液可以诱导成人上皮细胞进行EMT；α5β1整合素在与胶原接触的表面上被激活，包括正常情况下不表达整合素的顶端表面。在体内，对细胞环境的病理操作同样可能导致EMT。在我们给出的例子中，EMT产生的侵袭性转移癌细胞是最可怕的。有趣的是，无论是转移性细胞还是正常胚胎成纤维细胞，E-钙粘附素基因都能将它们转化为上皮表型。未来有可能操纵患病细胞的组织表型，使其对动物有利。
Epithelium is the tissue phenotype of early embryos and primitive adults of the chordate phylum. A second tissue type, however, is produced by epithelial-mesenchymal transformation (EMT) in higher chordates, such as vertebrata. Mesenchymal cells have the ability, which true epithelia do not, to invade and migrate through the extracellular matrix (ECM) to create dramatic cell transpositions. The first-formed or primary mesenchymal cells in amniote vertebrates migrate from the primitive streak to differentiate into the mesodermal and endodermal epithelia. Definitive mesenchyme with connective tissue and muscle potentials arises from the epithelial mesoderm at about the same time as the neural crest mesenchyme forms from the ectoderm. Later on in embryogenesis. EMT is used to remodel unwanted epithelia, such as that of the palate medial edges. We discuss the mechanisms by which epithelial cells transform into mesenchyme and vice versa. On the one hand, cells activate putative mesenchymal master genes, turn off epithelial genes, and acquire motility machinery that allows them to interact in 3 dimensions (3D) with ECM via actin cortex while sliding their endoplasm into their new front ends. On the other hand, primary mesenchymal cells can reactivate epithelial regulatory genes, such as E-cadherin, turn off the motility machinery for invading ECM, and reexpress apical-basal polarity. We review the genes, such as FSP1, src, ras, and fos, that are activated in cells transforming to mesenchyme and the genes their neighbors activate to induce EMT, such as those for TGF beta, NT-3, and sonic hedgehog. Suspension in 3D collagen gels can induce adult epithelium to undergo EMT; alpha 5 beta 1 integrin is activated on surfaces in contact with collagen, including apical surfaces that do not normally express integrins. In vivo, it is possible that pathological manipulations of a cell's environment likewise induce EMT. Of the examples we give, the creation of invasive metastatic carcinoma cells by EMT is the most fearful. Interestingly, transfection of either metastatic cells or normal embryonic fibroblasts with the E-cadherin gene converts them to the epithelial phenotype. It may be possible in the future to manipulate the tissue phenotype of diseased cells to the advantage of the animal.