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Compound Specifically Inhibits Tumor Vasculature

Endorepellin studied in mice; could lead to new means to fight cancer

TUESDAY, Nov. 28 (HealthDay News) -- The molecule endorepellin inhibits the growth of the vascular system of human skin and lung tumors in mice, opening up possibilities for a new type of cancer treatment, according to a report published in the Nov. 15 issue of the Journal of the National Cancer Institute.

Renato V. Iozzo, M.D., of Thomas Jefferson University in Philadelphia, and colleagues studied mice bearing orthotopic squamous carcinoma xenografts or syngeneic Lewis lung carcinoma tumors. The animals were treated with human recombinant endorepellin, which is a protein fragment from the heparan sulfate proteoglycan, perlecan.

Immuno-histochemical analysis revealed that endorepellin targets the vascular system of tumors and accumulates in the perivascular zones of the tumor. Compared with untreated controls, tumors in the treated mice showed significant reductions in angiogenesis, tumor metabolism and mitotic index, as well as enhanced tumor hypoxia. Tumor-derived endothelial cells internalize the molecule, where it causes a redistribution of α2β1 integrin, inhibiting its function in the perivascular region, the investigators found.

"Despite the need for further investigation for endorepellin's mechanism of action in vivo, endorepellin's ability to localize to the tumor vasculature and its seemingly selective interference with tumor capillarization represent a novel, additional tool that could be added to the anti-cancer therapeutic armamentarium," the authors conclude.

The study was funded with grants from the National Institutes of Health and the Commonwealth of Pennsylvania.

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