S Schmitmeier1, F S Markland, T C Chen. 1. Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine and Norris Comprehensive Cancer Center, Los Angeles, 1200 N. State St #5046, Los Angeles, CA 90033, USA.
Abstract
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.
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 humanglioblastoma 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.
Authors: Lucie Dardevet; Dipti Rani; Tarek Abd El Aziz; Ingrid Bazin; Jean-Marc Sabatier; Mahmoud Fadl; Elisabeth Brambilla; Michel De Waard Journal: Toxins (Basel) Date: 2015-03-27 Impact factor: 4.546
Authors: Leonardo A Calderon; Juliana C Sobrinho; Kayena D Zaqueo; Andrea A de Moura; Amy N Grabner; Maurício V Mazzi; Silvana Marcussi; Auro Nomizo; Carla F C Fernandes; Juliana P Zuliani; Bruna M A Carvalho; Saulo L da Silva; Rodrigo G Stábeli; Andreimar M Soares Journal: Biomed Res Int Date: 2014-02-13 Impact factor: 3.411