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: Zhifeng Liu, Xuejun Yang, Cong Chen, Bin Liu, Bingcheng Ren, Leilei Wang, Kai Zhao, Shengping Yu, Haolang Ming
• Journal: Oncology reports (Oncol Rep) Vol. 30 Issue 5 Pg. 2127-36 (Nov 2013) ISSN: 1791-2431 [Electronic] Greece
• PMID: 23969835 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actin-Related Protein 2-3 Complex
• Actins

Topics

• Actin-Related Protein 2-3 Complex (genetics)
• Actins (genetics, metabolism)
• Brain Neoplasms (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Polarity
• Dendritic Cells (pathology, ultrastructure)
• Gene Expression Regulation, Neoplastic
• Glioma (genetics, pathology)
• Humans
• Microscopy, Confocal
• Neoplasm Invasiveness (genetics)
• Pseudopodia (pathology, ultrastructure)