The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/12/2349/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 12, December 21, 1998 2349-2356


Articles

Vasostatin, a Calreticulin Fragment, Inhibits Angiogenesis and Suppresses Tumor Growth

Sandra E. Pike*, Lei Yao*, Karen D. Jones*, Barry Cherney*, Ettore Appella{ddagger}, Kazuyasu Sakaguchi{ddagger}, Hira Nakhasi*, Julie Teruya-Feldstein§, Peter Wirth||, Ghanshyam Gupta*, and Giovanna Tosato*

From the * Center for Biologics Evaluation and Research, Rockville, Maryland 20852; and the {ddagger} Laboratory of Cell Biology, the § Laboratory of Pathology, and the || Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892

An endothelial cell inhibitor was purified from supernatant of an Epstein-Barr virus–immortalized cell line and identified as fragments of calreticulin. The purified recombinant NH2-terminal domain of calreticulin (amino acids 1–180) inhibited the proliferation of endothelial cells, but not cells of other lineages, and suppressed angiogenesis in vivo. We have named this NH2-terminal domain of calreticulin vasostatin. When inoculated into athymic mice, vasostatin significantly reduced growth of human Burkitt lymphoma and human colon carcinoma. Compared with other inhibitors of angiogenesis, vasostatin is a small, soluble, and stable molecule that is easy to produce and deliver. As an angiogenesis inhibitor that specifically targets proliferating endothelial cells, vasostatin has a unique potential for cancer treatment.

Key Words: endothelial cells • angiogenesis • cell growth • cancer • antitumor agent


Address correspondence to Giovanna Tosato, Center for Biologics Evaluation and Research, Building 29A, Room 2D16, HFM535, 1401 Rockville Pike, Rockville, MD 20852-1448. Phone: 301-827-1794; Fax: 301-480-3256; E-mail: Tosato{at}A1.CBER.FDA.GOV

S.E. Pike and L. Yao contributed equally to this work.

Abbreviations used: aa, amino acids; bFGF, basic fibroblast growth factor; FBHE, fetal bovine heart endothelial cells; HUVEC, human umbilical vein endothelial cells; IP-10, IFN-{gamma} inducible protein-10; MBP, maltose-binding protein; Mig, monokine induced by IFN-{gamma}; VEGF, vascular endothelial growth factor.


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