Determinants of human astrocytoma migration.
Determinants of human astrocytoma migration.
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发表时间：
1994-07
期刊：
影响因子：
11.2
通讯作者：
A. Giese;Monique D. Rief;Melinda A. Loo;M. Berens
中科院分区：
文献类型：
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作者：
A. Giese;Monique D. Rief;Melinda A. Loo;M. Berens
星形细胞恶性肿瘤的一个独特特征是它们经常通过大脑传播。迁移的细胞决定因素包括对基质的粘附、肌动蛋白细胞骨架的重组以产生运动，以及（在侵入组织的情况下）分泌酶以重塑间隙空间以适应迁移细胞的向前运动。为了更好地理解星形细胞瘤细胞局部脑侵袭背景下的这些特征，在体外单层系统中研究了这些细胞的粘附和迁移特性。 8 种不同的星形细胞瘤细胞系与不同的纯化人细胞外基质 (ECM) 蛋白（IV 型胶原、细胞纤连蛋白、层粘连蛋白和玻连蛋白）的粘附表明，不存在始终导致高细胞结合的“星形细胞瘤特异性”ECM 蛋白。类似地，发现星形细胞瘤细胞的迁移是可变的并且依赖于不同的 ECM 蛋白。层粘连蛋白通常是最容易粘附和迁移的。对胶原蛋白、纤连蛋白和玻连蛋白的粘附是整合素依赖性的，并且可以使用抗 β1 整合素抗体来阻断；相反，使用这些抗体不能阻断与层粘连蛋白的附着。对每种细胞系在 4 种 ECM 蛋白上的粘附与迁移的比较表明，粘附力差与最小迁移相关，而高粘附力通常与快速迁移相关。当在自体细胞来源的 ECM 上进行迁移测试时，除了 SF767 细胞外，没有任何细胞系的迁移能力与在一种纯化的 ECM 蛋白上的迁移能力相同。此外，发现SF767细胞的ECM促进其他星形细胞瘤细胞的迁移。这项研究的结果表明，迁移是神经胶质瘤细胞的一种组成行为，它依赖于环境中允许配体的存在或不存在，或受其影响。
A unique characteristic of astrocytic malignancies is their frequent dissemination through the brain. Cellular determinants of migration include adhesion to the substratum, restructuring of the actin cytoskeleton to generate motion, and (in the setting of invasion into tissue) secretion of enzymes for remodeling interstitial space to accommodate forward motion of the migrating cell. In order to better understand these features in the context of local brain invasion by astrocytoma cells, the adhesion and migratory properties of these cells have been investigated in an in vitro monolayer system. Adhesion of 8 different astrocytoma cell lines to different purified human extracellular matrix (ECM) proteins (collagen type IV, cellular fibronectin, laminin, and vitronectin) revealed that there is no "astrocytoma-specific" ECM protein that consistently leads to high cell binding. Similarly, migration of astrocytoma cells was found to be variable and dependent on different ECM proteins. Laminin was frequently the most permissive for adhesion and migration. Adhesion to collagen, fibronectin, and vitronectin was integrin dependent and could be blocked using anti-beta 1 integrin antibodies; in contrast, attachment to laminin could not be blocked using these antibodies. A comparison of adhesion with migration for each of the cell lines on each of the 4 ECM proteins revealed that poor adhesion was associated with minimal migration and that frequently, high adhesion was correlated with rapid migration. When tested for migration on autologous, cell-derived ECM, none of the cell lines were as migratory as they were on one of the purified ECM proteins, with the exception of SF767 cells. Furthermore, it was found that ECM from SF767 cells promoted the migration of other astrocytoma cells. The results from this study indicate that migration is a constitutive behavior of glioma cells which is dependent on, or modified by, the presence or absence of permissive ligands in the environment.