Expression of the Arp2/3 complex in human gliomas and its role in the migration and invasion of glioma cells
Expression of the Arp2/3 complex in human gliomas and its role in the migration and invasion of glioma cells
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DOI：
10.3892/or.2013.2669
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发表时间：
2013-11-01
期刊：
影响因子：
4.2
通讯作者：
Ming, Haolang
中科院分区：
文献类型：
--
作者：
Liu, Zhifeng;Yang, Xuejun;Ming, Haolang
定向细胞迁移的一个标志是细胞前导突起处的局部肌动蛋白聚合。 Arp2/3 复合体在运动细胞前缘形成树突状肌动蛋白网络（片状伪足）。本研究旨在探讨 Arp2/3 复合物在神经胶质瘤细胞浸润行为中的作用。免疫荧光和蛋白质印迹显示Arp2/3的表达与胶质瘤标本的恶性程度呈正相关（r=0.686，P=0.02），共聚焦显微镜显示Arp2/3复合物定位于胶质瘤细胞的板状伪足中。此外，我们使用 Arp2/3 复合物抑制剂 CK666 检查了 Arp2/3 复合物抑制对 U251、LN229 和 SNB19 神经胶质瘤细胞的影响。用 CK666 处理后，神经胶质瘤细胞失去了片状伪足和细胞极性。 Arp2/3 复合物的抑制显着影响神经胶质瘤细胞迁移和侵袭的能力。在伤口愈合测定中，CK666显着抑制细胞迁移，U251细胞迁移被抑制至对照的38.73+/-3.45%，LN229细胞被抑制至对照的57.40+/-2.16%，SNB19细胞被抑制至对照的34.17+/-3.82%。此外，与 DMSO 对照相比，CK666 显着损害 U251、LN229 和 SNB19 细胞的 Transwell 小室侵袭能力，分别达 72.70 +/- 4.86、39.12 +/- 8.42 和 41.41 +/- 4.66%。因此，Arp2/3 复合体可能是神经胶质瘤细胞侵袭和迁移的关键参与者，并且可能代表治疗干预的靶点。
A hallmark of directional cell migration is localized actin polymerization at the leading protrusions of the cell. The Arp2/3 complex nucleates the formation of the dendritic actin network (lamellipodia) at the leading edge of motile cells. This study was designed to investigate the role of the Arp2/3 complex in the infiltrative behavior of glioma cells. Immunofluorescence and western blotting showed a positive correlation between the expression of Arp2/3 and the malignancy of glioma specimens (r=0.686, P=0.02) and confocal microscopy demonstrated localization of the Arp2/3 complex in lamellipodia of glioma cells. Furthermore, we examined the effects of Arp2/3 complex inhibition in U251, LN229 and SNB19 glioma cells using CK666, an Arp2/3 complex inhibitor. Glioma cells lost lamellipodia and cell polarity after treatment with CK666. Inhibition of the Arp2/3 complex significantly affected the ability of glioma cells to migrate and invade. In the wound-healing assay, CK666 markedly inhibited cell migration, U251 cell migration was inhibited to 38.73 +/- 3.45% of control, LN229 cells to 57.40 +/- 2.16% of control and SNB19 cells to 34.17 +/- 3.82% of control. Also, CK666 significantly impaired Transwell chamber invasion capability of U251, LN229 and SNB19 cells compared with DMSO control by 72.70 +/- 4.86, 39.12 +/- 8.42 and 41.41 +/- 4.66%, respectively. The Arp2/3 complex is, therefore, likely to be a crucial participant in glioma cell invasion and migration, and may represent a target for therapeutic intervention.