Integrin α3β1 engagement disrupts intercellular adhesion
Integrin α3β1 engagement disrupts intercellular adhesion
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DOI：
10.1006/excr.2000.5083
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发表时间：
2001-01-15
影响因子：
3.7
通讯作者：
Kramer, RH
中科院分区：
文献类型：
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作者：
Kawano, K;Kantak, SS;Kramer, RH
在组织形态发生和肿瘤侵袭期间，上皮细胞必须经历细胞间重排，其中细胞相对于彼此和周围间充质细胞外基质重新定位。使用三维聚集的鳞状上皮细胞，我们表明，这种细胞间重排可以触发激活β 1整合素后，他们与细胞外基质连接。在非粘附基质上，多细胞聚集体（MCA）通过E-钙粘蛋白连接复合物迅速形成，并随着时间的推移成为致密的球体，表现出更多的上皮表型。在将MCA重新接种在培养基质上后，球状体塌陷以产生紧密排列的细胞单层。细胞-细胞接触诱导E-钙粘蛋白水平的快速升高，这是由于连接受体的代谢稳定性增加。在MCA重塑细胞-细胞粘附和单层形成过程中，它们的E-钙粘蛋白水平迅速下降。无论哪种ECM配体-I型胶原蛋白、纤连蛋白或层粘连蛋白1-MCAs. In相比之下，当接种到由鳞状上皮细胞精心制作的基质上时，MCA中的细胞附着、扩散、失去细胞-细胞连接并分散，都获得了类似的行为。分析确定层粘连蛋白5是该基质中的活性ECM配体，MCA分散需要功能性β 1整联蛋白，特别是α 3 β 1。此外，底物固定的抗整合素抗体有效地再现了层粘连蛋白5基质诱导的上皮-间充质样转化。在早期阶段的聚集体重排和崩溃，层粘连蛋白5基板上的细胞，但不是那些胶原蛋白I基板上，表现出强烈的皮质阵列的F-肌动蛋白，微刺，和肌成束蛋白积累在其外周表面。这些结果表明，特定的整合素-配体对的参与调节上皮形态发生和肿瘤侵袭过程中常见的钙粘蛋白连接粘连。(C)北京：科学出版社.
During tissue morphogenesis and tumor invasion, epithelial cells must undergo intercellular rearrangement in which cells are repositioned with respect to one another and the surrounding mesenchymal extracellular matrix. Using three-dimensional aggregates of squamous epithelial cells, we show that such intercellular rearrangements can be triggered by activation of beta1 integrins after their ligation with extracellular matrices. On nonadherent substrates, multicellular aggregates (MCAs) formed rapidly via E-cadherin junctional complexes and over time became compacted spheroids exhibiting a more epithelial phenotype. After MCAs were replated on culture substrates, the spheroids collapsed to yield tightly arranged cell monolayers. Cell-cell contact induced rapid elevation in E-cadherin levels, which was due to an increase in the metabolic stability of junctional receptors. During MCA remodeling of cell-cell adhesions, and monolayer formation, their E-cadherin levels fell rapidly. Similar behavior was obtained regardless of which ECM ligand-collagen type I, fibronectin, or laminin 1-MCAs were seeded on. In contrast, when seeded onto a matrix elaborated by squamous epithelial cells, cells in the MCA attached, spread, lost cell-cell junctions, and dispersed. Analysis identified laminin 5 as the active ECM ligand in this matrix, and MCA dispersion required functional beta1 integrin and specifically alpha3 beta1. Furthermore, substrate-immobilized anti-integrin antibody effectively reproduced the epithelial-mesenchymal-like transition induced by the laminin 5 matrix. During the early stages of aggregate rearrangement and collapse, cells on laminin 5 substrates, but not those on collagen I substrates, exhibited intense cortical arrays of F-actin, microspikes, and fascin accumulation at their peripheral surfaces. These results suggest that engagement of specific integrin-ligand pairs regulates cadherin junctional adhesions during events common to epithelial morphogenesis and tumor invasion. (C) 2001 Academic Press.