The role of contortrostatin, a snake venom disintegrin, in the inhibition of tumor progression and prolongation of survival in a rodent glioma model.
OBJECTIVE
Malignant gliomas are not curable because of diffuse brain invasion. The tumor cells invade the surrounding brain tissue without a clear tumor-brain demarcation line, making complete resection impossible. Therapy aimed at inhibition of invasion is crucial not only for prevention of tumor spread, but also for selectively blocking migrating cells that may be more resistant to chemotherapy and radiation. Recently, investigations have shown that the snake venom disintegrin contortrostatin specifically binds to certain integrins on the surface of glioma cells and thereby inhibits their interaction with the extracellular matrix (ECM), resulting in a blockage of cell motility and invasiveness. To translate these in vitro findings into clinical settings, the authors examined the effect of contortrostatin on glioma progression in a rodent model.


METHODS
Athymic mice were intracranially or subcutaneously injected with U87 glioma cells, and the effect of intratumorally administered contortrostatin on tumor progression and animal survival was then studied. In addition, the authors evaluated the pharmacological safety of contortrostatin use in the brains of tumor-free animals.


CONCLUSIONS
The results demonstrate that contortrostatin is able to inhibit tumor growth and angiogenesis and to prolong survival in a rodent glioma model. Moreover, contortrostatin appears to be well tolerated by the animal and lacks obvious neurotoxic side effects. Thus, contortrostatin may have potential as a novel therapeutic agent for the treatment of malignant gliomas.
Pyrko
Peter
P
Department of Neurosurgery, University of Southern California, Keck School of Medicine, Los Angeles, California 90033, USA.
Wang
Weijun
W
Markland
Francis S
FS
Swenson
Steve D
SD
Schmitmeier
Stephanie
S
Schönthal
Axel H
AH
Chen
Thomas C
TC
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D019483:Disintegrins / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis
D019483:Disintegrins; C403494:contortrostatin