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Calreticulin and calreticulin fragments are endothelial cell inhibitors that suppress tumor growth.
- Source :
-
Blood [Blood] 1999 Oct 01; Vol. 94 (7), pp. 2461-8. - Publication Year :
- 1999
-
Abstract
- 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.
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Burkitt Lymphoma drug therapy
Calcium-Binding Proteins chemistry
Calcium-Binding Proteins therapeutic use
Calreticulin
Cattle
Cell Division drug effects
Cells, Cultured
Endothelium, Vascular cytology
Endothelium, Vascular drug effects
Female
Heart
Humans
Mice
Mice, Nude
Neovascularization, Pathologic pathology
Neovascularization, Pathologic prevention & control
Peptide Fragments therapeutic use
Recombinant Proteins pharmacology
Ribonucleoproteins chemistry
Ribonucleoproteins therapeutic use
Transplantation, Heterologous
Tumor Cells, Cultured
Angiogenesis Inhibitors pharmacology
Antineoplastic Agents therapeutic use
Burkitt Lymphoma pathology
Calcium-Binding Proteins pharmacology
Calcium-Binding Proteins toxicity
Endothelium, Vascular physiology
Neovascularization, Physiologic drug effects
Peptide Fragments pharmacology
Peptide Fragments toxicity
Ribonucleoproteins pharmacology
Ribonucleoproteins toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 94
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 10498619