Hay E D
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Acta Anat (Basel). 1995;154(1):8-20. doi: 10.1159/000147748.
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.
上皮组织是脊索动物门早期胚胎和原始成体的组织表型。然而，在高等脊索动物（如脊椎动物）中，第二种组织类型是通过上皮-间充质转化（EMT）产生的。间充质细胞具有真正上皮细胞所没有的能力，即侵入并穿过细胞外基质（ECM）进行迁移，从而导致显著的细胞移位。羊膜动物脊椎动物中最早形成的或原始的间充质细胞从原条迁移，分化为中胚层和内胚层上皮。具有结缔组织和肌肉潜能的确定间充质大约在神经嵴间充质从外胚层形成的同时，由上皮中胚层产生。在胚胎发育后期，EMT被用于重塑不需要的上皮组织，比如腭内侧边缘的上皮组织。我们讨论上皮细胞转化为间充质细胞以及反之亦然的机制。一方面，细胞激活假定的间充质主控基因，关闭上皮基因，并获得运动机制，使它们能够通过肌动蛋白皮质在三维（3D）空间中与ECM相互作用，同时将其内质滑入新的前端。另一方面，原始间充质细胞可以重新激活上皮调节基因，如E-钙黏蛋白，关闭侵入ECM的运动机制，并重新表达顶端-基部极性。我们综述了在转化为间充质细胞的细胞中被激活的基因，如FSP1、src、ras和fos，以及其邻近细胞激活以诱导EMT的基因，如转化生长因子β、神经营养因子-3和音猬因子的基因。悬浮在3D胶原凝胶中可诱导成年上皮细胞发生EMT；α5β1整合素在与胶原接触的表面被激活，包括通常不表达整合素的顶端表面。在体内，细胞环境的病理操作同样可能诱导EMT。在我们给出的例子中，通过EMT产生侵袭性转移性癌细胞是最可怕的。有趣的是，用E-钙黏蛋白基因转染转移性细胞或正常胚胎成纤维细胞会将它们转化为上皮表型。未来有可能将患病细胞的组织表型调节到对动物有利的状态。
