Role of intracellular S100A4 for migration of rat astrocytes
Role of intracellular S100A4 for migration of rat astrocytes
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DOI：
10.1002/glia.20284
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发表时间：
2006-02
期刊：
影响因子：
6.2
通讯作者：
K. Takenaga;E. Kozlova
中科院分区：
文献类型：
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作者：
K. Takenaga;E. Kozlova
S100A4是EF-Hand钙结合蛋白家族的成员，最先在肿瘤细胞中发现，并与肿瘤的侵袭和转移有关。S100A4在细胞内的上调与肿瘤细胞的运动性增加有关。细胞外应用S100A4可增加胶质瘤细胞的体外运动能力。我们之前的研究表明，脊髓和脑白质中的星形胶质细胞也表达S100A4。这种表达在损伤后反应性白质星形胶质细胞中显著增加。在这里，我们探索了细胞内S100A4的变化如何影响星形胶质细胞的迁移。我们培养了表达S100A4的星形胶质细胞，并建立了一种小干扰(Si)RNA方法来特异性地消除这些细胞中S100A4的表达，并比较了表达S100A4的星形胶质细胞和转导S100A4 siRNA的星形胶质细胞的迁移情况。作为“阳性对照”，我们使用了表达C6的胶质瘤细胞S100A4。与恶性细胞相比，表达S100A4的星形胶质细胞经S100A4 siRNA处理后，其迁移能力增强。与此同时，随着迁移的增加，白质星形胶质细胞增加了其金属蛋白酶MMP9和MT1 MMP2的表达。加入MMP2/MMP9抑制剂后，S100A4 siRNA处理的星形胶质细胞迁移受到明显抑制。这些发现表明，S100A4在反应性白质星形胶质细胞中具有稳定功能，这一功能可能有助于硬性、生长抑制的胶质瘢痕的发展。©2005 Wiley-Liss Inc.
S100A4 is a member of the EF‐hand family of calcium‐binding proteins, first identified in tumor cells, and implicated in tumor invasion and metastasis. Intracellular upregulation of S100A4 is associated with increased motility of tumor cells. Extracellular application of S100A4 increases the motility of glioma cells in vitro. We showed previously that astrocytes in spinal cord and brain white matter also express S100A4. This expression is markedly increased in reactive white matter astrocytes after injury. Here, we have explored how changes in intracellular S100A4 affect migration of astrocytes. We produced cultures of white matter, S100A4 expressing astrocytes, and developed a small interfering (si) RNA approach to specifically eliminate S100A4 expression in these cells, and compared the migration of astrocytes expressing S100A4 with astrocytes transfected with S100A4 siRNA. As a “positive control” we used S100A4 expressing C6 glioma cells. In contrast to malignant cells, S100A4 expressing astrocytes increased their migration capacity after S100A4 siRNA treatment. At the same time, and in parallel with increased migration, white matter astrocytes increased their expression of metalloproteinases MMP‐9 and MT1‐MMP. The addition of MMP‐2/MMP‐9 inhibitor resulted in a significant inhibition of migration in S100A4 siRNA‐treated astrocytes. These findings indicate that S100A4 has a stabilizing function in reactive white matter astrocytes, a function that may contribute to the development of a rigid, growth‐inhibitory glial scar. © 2005 Wiley‐Liss, Inc.