Extracellular S100A4 stimulates the migration rate of astrocytic tumor cells by modifying the organization of their actin cytoskeleton
Extracellular S100A4 stimulates the migration rate of astrocytic tumor cells by modifying the organization of their actin cytoskeleton
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DOI：
10.1016/s1570-9639(02)00447-8
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发表时间：
2002-11-04
影响因子：
3.2
通讯作者：
Decaestecker, C
中科院分区：
文献类型：
--
作者：
Belot, N;Pochet, R;Decaestecker, C
在以前的研究中，我们已经表明，S100钙结合蛋白（包括S100 A4）的数量在星形细胞肿瘤中的表达差异，根据其恶性程度。S100 A4参与肿瘤进展、细胞迁移和转移。这种蛋白能够发挥细胞外作用，如神经生和血管生成活性。本研究旨在探讨细胞外S100 A4在星形胶质细胞肿瘤细胞体外迁移中可能发挥的作用。使用计算机辅助视频显微镜测量活细胞迁移的速度和速率。同时，我们还分析了细胞外S100 A4对肌动蛋白细胞骨架组织及其一些分子调节因子表达的影响。这些包括小Rho-GTP酶（RhoA，Rac 1和Cdc 42）和它们的一些直接效应物（mDia和N-WASP），以及肌动蛋白结合蛋白，如profilin和a-actinin。我们的数据证明了S100 A4对星形胶质细胞肿瘤细胞在这些不同方面的影响。事实上，我们表明，细胞外S100 A4治疗降低这两个。聚合的F-肌动蛋白的量和RhoA、mDia和profilin的表达水平。虽然也观察到Cdc 42和N-WASP表达减少，但Rac 1表达保持不变。所有这些活动，导致刺激细胞运动，有助于理解S100 A4的细胞外作用。(C)2002 Elsevier Science B.V保留所有权利。
In previous studies, we have shown that numbers of S100 calcium-binding proteins (including S100A4) are expressed differentially in astrocytic tumors according to their levels of malignancy. S100A4 is involved in tumor progression, cell migration and metastasis. This protein is able to play extracellular roles such as neuritogenic and angiogenic activities. The present study aims to investigate the possible role played by extracellular S100A4 in the in vitro migration of astrocytic tumor cells. The speed and rate of migration of living cells were measured using computer-assisted videomicroscopy. In parallel, we also analyzed the effects of extracellular S100A4 on the organization of the actin cytoskeleton and the expression of a number of its molecular regulators. These included small Rho-GTPases (RhoA, Rac1 and Cdc42) and some of their direct effectors (mDia and N-WASP), and also actin-binding proteins such as profilin and a-actinin. Our data demonstrate the influence of S100A4 on astrocytic tumor cells with respect to these different aspects. Indeed, we show that extracellular S100A4 treatments decrease both the. amount of polymerized F-actin and the levels of expression of RhoA, mDia and profilin. While a decrease in the Cdc42 and N-WASP expression was also observed, the Rac1 expression remained unchanged. All these activities, which result in the stimulation of cell motility, contribute to the understanding of the extracellular role of S100A4. (C) 2002 Elsevier Science B.V All rights reserved.