title: Expression of the Arp2/3 complex in human gliomas and its role in the migration and invasion of glioma cells.
abstract: 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.
authors: Neuro-Oncology Laboratory, Tianjin Neurological Institute, Tianjin 300052, P.R. China.
authors: Zhifeng
authors: Z
authors: Liu
authors: Xuejun
authors: X
authors: Yang
authors: Cong
authors: C
authors: Chen
authors: Bin
authors: B
authors: Liu
authors: Bingcheng
authors: B
authors: Ren
authors: Leilei
authors: L
authors: Wang
authors: Kai
authors: K
authors: Zhao
authors: Shengping
authors: S
authors: Yu
authors: Haolang
authors: H
authors: Ming
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics*; D000199:Actins / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity; D003713:Dendritic Cells / Q000473:pathology / Q000648:ultrastructure; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011554:Pseudopodia / Q000473:pathology / Q000648:ultrastructure
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins