title: Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth.
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-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.
authors.affiliation: Center for Biologics Evaluation and Research, Rockville, Maryland 20852, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Pike
authors.forename: L
authors.initials: L
authors.lastname: Yao
authors.forename: K D
authors.initials: KD
authors.lastname: Jones
authors.forename: B
authors.initials: B
authors.lastname: Cherney
authors.forename: E
authors.initials: E
authors.lastname: Appella
authors.forename: K
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: H
authors.initials: H
authors.lastname: Nakhasi
authors.forename: J
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: P
authors.initials: P
authors.lastname: Wirth
authors.forename: G
authors.initials: G
authors.lastname: Gupta
authors.forename: G
authors.initials: G
authors.lastname: Tosato
mesh_terms: D000818:Animals; D002051:Burkitt Lymphoma / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D037282:Calreticulin; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D003110:Colonic Neoplasms / Q000473:pathology; D017077:Culture Media, Conditioned; D004727:Endothelium / Q000166:cytology / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009374:Neoplasms, Experimental / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012261:Ribonucleoproteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology / Q000196:embryology
chemical_list: D002135:Calcium-Binding Proteins; D037282:Calreticulin; D017077:Culture Media, Conditioned; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D016222:Fibroblast Growth Factor 2