J. Exp. Med., Volume 188, Number 12, December 21, 1998 2349-2356

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

By Sandra E. Pike,^* Lei Yao,^* Karen D. Jones,^* Barry Cherney,^* Ettore Appella, Kazuyasu Sakaguchi, 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  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.

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