Anti-invasive effect of contortrostatin, a snake venom disintegrin, and TNF-alpha on malignant glioma cells.

BACKGROUND

The snake venom disintegrin contortrostatin has been shown to bind to integrins alpha IIb beta 3, alpha v beta 3, alpha v beta 5, and alpha 5 beta 1 and to exert an anti-tumor activity in vitro and in vivo. The cytokine TNF-alpha has been demonstrated to have anti-invasive properties in vitro.

MATERIALS AND METHODS

The human glioblastoma cell line T98G was treated with controtrostatin or colloidal gold-TNF-alpha (CG-TNF-alpha) alone, or in combination. Vitronectin- and fibronectin-dependent adhesion of untreated and treated glioma cells was studied and compared. Invasion through a reconstituted basement membrane (Matrigel) was also examined.

RESULTS

Although both contortrostatin and CG-TNF-alpha inhibited invasion of T98G cells through Matrigel, the mechanism of inhibition appears to be different. Contortrostatin significantly decreased cell adhesion to vitronectin and fibronectin; CG-TNF-alpha did not. Contortrostatin binds to T98G integrins in an RGD-dependent manner, whereas protein kinase C (PKC) appears to be involved in CG-TNF-alpha actions, leading to inhibition of cell invasion. The efficiency of contortrostatin in inhibiting cell invasion was enhanced by combination with CG-TNF-alpha.

CONCLUSION

The combined use of contortrostatin and CG-TNF-alpha may have potential for malignant glioma therapy by effectively inhibiting glioma cell invasion.