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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21 December 1998
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December 21 1998
Vasostatin, a Calreticulin Fragment, Inhibits Angiogenesis and Suppresses Tumor Growth
Sandra E. Pike,
Sandra E. Pike
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
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Lei Yao,
Lei Yao
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
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Karen D. Jones,
Karen D. Jones
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
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Barry Cherney,
Barry Cherney
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
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Ettore Appella,
Ettore Appella
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
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Kazuyasu Sakaguchi,
Kazuyasu Sakaguchi
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
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Hira Nakhasi,
Hira Nakhasi
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
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Julie Teruya-Feldstein,
Julie Teruya-Feldstein
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
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Peter Wirth,
Peter Wirth
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
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Ghanshyam Gupta,
Ghanshyam Gupta
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
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Giovanna Tosato
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
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Sandra E. Pike
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
Lei Yao
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
Karen D. Jones
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
Barry Cherney
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
Ettore Appella
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
Kazuyasu Sakaguchi
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
Hira Nakhasi
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
Julie Teruya-Feldstein
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
Peter Wirth
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
Ghanshyam Gupta
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
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
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: [email protected]
S.E. Pike and L. Yao contributed equally to this work.
Received:
September 02 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (12): 2349–2356.
Article history
Received:
September 02 1998
Citation
Sandra E. Pike, Lei Yao, Karen D. Jones, Barry Cherney, Ettore Appella, Kazuyasu Sakaguchi, Hira Nakhasi, Julie Teruya-Feldstein, Peter Wirth, Ghanshyam Gupta, Giovanna Tosato; Vasostatin, a Calreticulin Fragment, Inhibits Angiogenesis and Suppresses Tumor Growth . J Exp Med 21 December 1998; 188 (12): 2349–2356. doi: https://doi.org/10.1084/jem.188.12.2349
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