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The aim of the present study was to investigate the role of cortactin in the infiltrative behavior of glioma cells and the potential mechanism of cortactin in promoting the migration and invasion of glioma cells. The expression of cortactin was detected by immunohistochemistry in 40 human glioma specimens and 8 non-tumor brain specimens. U251, LN229 and SNB19 glioma cells were employed for the in vitro study and assigned into the siRNA-cortactin (transfected with siRNA specific to cortactin), siRNA-NC (transfected with negative control RNA sequence) and siRNA-N (transfected with empty vector) groups. The expression of cortactin in different treated glioma cell groups was detected using western blot analysis and RT-qPCR. The migration and invasion of glioma cells under different treatments were assessed using a wound-healing assay and Transwell-chamber invasion assay, respectively. The lamellipodia of glioma cells following treatment were observed by immunofluorescence (IF) and changes of lamellipodia over time were imaged using an inverted microscope. The distribution of cortactin and the actin-related protein 2/3 (Arp2/3) complex in glioma cells were observed after IF detection. The expression of cortactin in the glioma specimens was significantly higher than that in non-tumor brain tissue (P

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.