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Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth

By Ra E. Pike, Lei Yao, Karen D. Jones, Barry Cherney, Kazuyasu Sakaguchi, Hira Nakhasi, Julie Teruya-feldstein, Peter Wirth, Ghanshyam Gupta and Giovanna Tosato

Abstract

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-termi nal 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 Tumor growth and invasion into normal tissues are dependent upon an adequate blood supply (1, 2). Agents that reduce tumor blood supply prevent or delay tumor formation, and promote the regression or dormancy of established tumors. Antibodies against vascular endothelial growth factor (VEGF), 1 which is produced at high levels by various types of tumors, antibodies against VEGF recepto

Year: 1998
OAI identifier: oai:CiteSeerX.psu:10.1.1.316.3053
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