Mar. 25, 2010 Dr. Roy L Silverstein and colleagues of the Cleveland Clinic, Cleveland, OH have identified HRGP as a new therapeutic target for anti-angiogenic cancer therapies.
These results are presented in the April 2010 issue of the American Journal of Pathology.
Glioblastoma, which is the most common and aggressive form of brain tumor in humans, occurs in 2-3 per 100,000 people in the Europe and North America. Inhibiting angiogenesis, or new blood vessel growth, is a major therapeutic strategy for glioblastoma.
Interaction of CD36, a cell surface receptor expressed on the cells that line small blood vessels, with a secreted portion of brain angiogenesis inhibitor 1 (Vstat120) elicits an anti-angiogenic response. Klenotic et al discovered that Vstat120 binding to CD36 activated a pro-apoptotic (cell death-inducing) pathway, which could be blocked by HRGP through HRGP-Vstat120 binding. The HRGP-Vstat120 interaction restored endothelial cell migration and tube formation and increased brain tumor growth with corresponding increases in tumor blood vessel development. Indeed, HRGP expression levels were increased in human brain cancers, indicating that this angiogenic axis could provide a therapeutic target for anti-angiogenic cancer therapies.
The study by Klenotic et al suggests that "in conditions where neo-vasculature is poorly organized and "leaky," such as in tumor beds, or where platelet activation occurs, such as in a wound or inflammatory site, HRGP can accumulate in the extracellular matrix and abrogate the potent anti-angiogenic activity of a broad class of angiogenesis inhibitors."
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- P. A. Klenotic, P. Huang, J. Palomo, B. Kaur, E. G. Van Meir, M. A. Vogelbaum, M. Febbraio, C. L. Gladson, R. L. Silverstein. Histidine-Rich Glycoprotein Modulates the Anti-Angiogenic Effects of Vasculostatin. American Journal Of Pathology, 2010; DOI: 10.2353/ajpath.2010.090782
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