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哺乳动物癌细胞趋化反应过程中突起形状的调节及与基质的黏附

Regulation of protrusion shape and adhesion to the substratum during chemotactic responses of mammalian carcinoma cells.

作者信息

Bailly M, Yan L, Whitesides G M, Condeelis J S, Segall J E

机构信息

Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461, USA.

出版信息

Exp Cell Res. 1998 Jun 15;241(2):285-99. doi: 10.1006/excr.1998.4031.

DOI:10.1006/excr.1998.4031
PMID:9637770
Abstract

We report here the first direct observation of chemotaxis to EGF by rat mammary carcinoma cells. When exposed to a gradient of EGF diffusing from a micropipette, MTLn3 cells displayed typical ameboid chemotaxis, extending a lamellipod-like protrusion and moving toward the pipette. Using a homogeneous upshift in EGF to model stimulated lamellipod extension (J. E. Segall et al., 1996, Clin. Exp. Metastasis 14, 61-72), we analyzed the relationship between adhesion and chemoattractant-stimulated protrusion. Exposure to EGF led to a rapid remodeling of the adhesive contacts on adherent cells, in synchrony with extension of a flat lamellipod over the substratum. EGF-stimulated lamellipods still extended in the presence of adhesion-blocking peptides or over nonadhesive surfaces. They were, however, slightly shorter and retracted rapidly under those conditions. The major protrusive structure observed on well-spread, adherent cells, after EGF stimulation was a flat broad lamellipod, whether or not in contact with the substratum, while cells in suspension showed transient protrusive activity over the entire cell surface. We conclude that the initial adhesive status of the cell conditions the shape of the outcoming protrusion. Altogether our results suggest that, although adhesive contacts are not necessary for lamellipod extension, they play a role in stabilizing the protrusion as well as in the control of its final shape and amplitude.

摘要

我们在此报告首次对大鼠乳腺癌细胞向表皮生长因子(EGF)的趋化作用进行的直接观察。当暴露于从微量移液器扩散出的EGF梯度中时,MTLn3细胞表现出典型的阿米巴样趋化作用,伸出类似片状伪足的突起并向移液器移动。我们使用EGF的均匀上调来模拟受刺激的片状伪足延伸(J.E.西格尔等人,1996年,《临床与实验转移》14卷,61 - 72页),分析了黏附与趋化因子刺激的突起之间的关系。暴露于EGF会导致贴壁细胞上的黏附接触迅速重塑,与在基质上平坦片状伪足的延伸同步。在存在黏附阻断肽的情况下或在非黏附表面上,EGF刺激的片状伪足仍会延伸。然而,在这些条件下它们会稍短一些并迅速缩回。EGF刺激后,在铺展良好的贴壁细胞上观察到的主要突出结构是一个平坦宽阔的片状伪足,无论是否与基质接触,而悬浮细胞在整个细胞表面显示出短暂的突出活性。我们得出结论,细胞的初始黏附状态决定了即将出现的突起的形状。总之,我们的结果表明,尽管黏附接触对于片状伪足的延伸不是必需的,但它们在稳定突起以及控制其最终形状和幅度方面发挥作用。

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