HSP27 mediates SPARC-induced changes in glioma morphology, migration, and invasion
HSP27 mediates SPARC-induced changes in glioma morphology, migration, and invasion
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DOI：
10.1002/glia.20679
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发表时间：
2008-08-01
期刊：
影响因子：
6.2
通讯作者：
Rempel, Sandra A.
中科院分区：
文献类型：
--
作者：
Golembieski, William A.;Thomas, Stacey L.;Rempel, Sandra A.
富含半胱氨酸的酸性分泌蛋白调节细胞-细胞外基质相互作用，影响细胞粘附和迁移。我们已经证明，在人脑胶质瘤中，hepatocellular carcinoma是高度表达的，它在体外和体内促进脑肿瘤的侵袭。为了进一步了解GFP在胶质瘤迁移中的作用，我们将GFP和GFP转染入U87 MG细胞，并在24 h后评估GFP对细胞形态、迁移和侵袭的影响。表达与细胞形态延长、迁移和侵袭增加有关。从0至6 h和24 h评估了E2对下游信号传导的影响。HSP 27的磷酸化水平增加，后者之前激活p38 MAPK和抑制p38 MAPK抑制剂S13203580。HSP 27 mRNA表达水平的增加与HSP 27 mRNA表达水平的增加相关。在一组神经胶质瘤细胞系中，增加的HSP 27水平与增加的总HSP 27和磷酸化HSP 27相关。HSP 27和HSP 27在体内共定位于入侵细胞。HSP 27 mRNA的抑制逆转了SPARC诱导的细胞形态、迁移和体外侵袭的变化。这些数据表明，热休克蛋白27，调节肌动蛋白聚合，细胞收缩和迁移的蛋白质，是一种新的下游效应的SPARC调节细胞形态和迁移。因此，它是一个潜在的治疗靶点，以抑制SPARC诱导的胶质瘤侵袭。(c)2008 Wiley-Liss，Inc.
Secreted protein acidic and rich in cysteine (SPARC) regulates cell-extracellular matrix interactions that influence cell adhesion and migration. We have demonstrated that SPARC is highly expressed in human gliomas, and it promotes brain tumor invasion in vitro and in vivo. To further our understanding regarding SPARC function in glioma migration, we transfected SPARC-green fluorescent protein (GFP) and control GFP vectors into U87MG cells, and assessed the effects of SPARC on cell morphology, migration, and invasion after 24 h. The expression of SPARC was associated with elongated cell morphology, and increased migration and invasion. The effects of SPARC on downstream signaling were assessed from 0 to 6 h and 24 h. SPARC increased the levels of total and phosphorylated HSP27; the latter was preceded by activation of p38 MAPK and inhibited by the p38 MAPK inhibitor S13203580. Augmented expression of SPARC was correlated with increased levels of HSP27 mRNA. In a panel of glioma cell lines, increasing levels of SPARC correlated with increasing total and phosphorylated HSP27. SPARC and HSP27 were colocalized to invading cells in vivo. Inhibition of HSP27 mRNA reversed the SPARC-induced changes in cell morphology, migration, and invasion in vitro. These data indicate that HSP27, a protein that regulates actin polymerization, cell contraction, and migration, is a novel downstream effector of SPARC-regulated cell morphology and migration. As such, it is a potential therapeutic target to inhibit SPARCinduced glioma invasion. (c) 2008 Wiley-Liss, Inc.