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Blood, Vol. 94 No. 7 (October 1), 1999:
pp. 2461-2468
Calreticulin and Calreticulin Fragments Are Endothelial Cell
Inhibitors That Suppress Tumor Growth
Sandra E. Pike,
Lei Yao,
Joyce Setsuda,
Karen D. Jones,
Barry Cherney,
Ettore Appella,
Kazuyasu Sakaguchi,
Hira Nakhasi,
Chintamani
D. Atreya,
Julie Teruya-Feldstein,
Peter Wirth,
Ghanshyam Gupta, and
Giovanna Tosato
From the Center for Biologics Evaluation and Research,
Rockville; the Laboratory of Cell Biology,
National Cancer Institute, DBS, Bethesda;
the Laboratory of Pathology, National Cancer
Institure, DCS, Bethesda; and the Laboratory of
Experimental Carcinogenesis, National Cancer Institute, DBS,
Bethesda, MD.
Several angiogenesis inhibitors are fragments of larger proteins
that are themselves not active as angiogenesis inhibitors. Vasostatin,
the N-terminal domain of calreticulin inclusive of amino acids 1-180, is an angiogenesis inhibitor that exerts antitumor effects in vivo. In
the present study, we examined whether the full-length calreticulin
molecule shares the antiangiogenic and antitumor activities of
vasostatin. Similar to vasostatin, calreticulin selectively inhibited
endothelial cell proliferation in vitro, but not cells of other
lineages, and suppressed angiogenesis in vivo. When inoculated into
athymic mice, calreticulin inhibited Burkitt tumor growth comparably
with vasostatin. Calreticulin lacking the N-terminal 1-120 amino acids
inhibited endothelial cell proliferation in vitro and Burkitt tumor
growth in vivo comparably with vasostatin. An internal calreticulin
fragment encompassing amino acids 120-180 also inhibited endothelial
cell proliferation in vitro and angiogenesis in vivo comparably with
calreticulin and vasostatin. These results suggest that the
antiangiogenic activities of vasostatin reside in a domain that is
accessible from the full-length calreticulin molecule and localize to
calreticulin N-terminal amino acids 120-180. Thus, calreticulin and
calreticulin fragments are inhibitors of angiogenesis that directly
target endothelial cells, inhibit angiogenesis, and suppress tumor
growth. This information may be critical in designing targeted
inhibitors of pathological angiogenesis that underlies cancer and other diseases.

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|
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|