Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth.
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.
Pike
S E
SE
Center for Biologics Evaluation and Research, Rockville, Maryland 20852, USA.
Yao
L
L
Jones
K D
KD
Cherney
B
B
Appella
E
E
Sakaguchi
K
K
Nakhasi
H
H
Teruya-Feldstein
J
J
Wirth
P
P
Gupta
G
G
Tosato
G
G
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
D002135:Calcium-Binding Proteins; D037282:Calreticulin; D017077:Culture Media, Conditioned; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D016222:Fibroblast Growth Factor 2