Angioarrestin: an antiangiogenic protein with tumor-inhibiting properties.
The angiopoietins comprise a family of proteins that have pro or antiangiogenic activities. Through a proprietary technology designed to identify transcripts of all expressed genes, we isolated a cDNA encoding an angiopoietin-related protein that we designate angioarrestin. The mRNA expression profile of angioarrestin was striking in that it was down-regulated in many tumor tissues when compared with adjacent nontumor tissue, suggesting a role for this protein in tumor inhibition. To test this hypothesis, we ectopically expressed angioarrestin in HT1080 tumor cells and measured pulmonary tumor nodule formation in nude mice. HT1080 cells expressing angioarrestin showed a marked reduction in the number and size of tumor nodules. In vitro, the recombinant protein was systematically tested in a number of endothelial cell assays and found to block critical processes involved in the angiogenic cascade, such as vascular endothelial growth factor/basic fibroblast growth factor-mediated endothelial cell proliferation, migration, tubular network formation, and adhesion to extracellular matrix proteins. These findings reveal a novel function for angioarrestin as an angiogenesis inhibitor and indicate that the molecule may be a potential cancer therapeutic.
Dhanabal
Mohanraj
M
CuraGen Corp., Branford, Connecticut 06405, USA.
LaRochelle
William J
WJ
Jeffers
Michael
M
Herrmann
John
J
Rastelli
Luca
L
McDonald
William F
WF
Chillakuru
Rajeev A
RA
Yang
Meijia
M
Boldog
Ferenc L
FL
Padigaru
Muralidhara
M
McQueeney
Kelly D
KD
Wu
Frank
F
Minskoff
Stacey A
SA
Shimkets
Richard A
RA
Lichenstein
Henri S
HS
D016475:3T3 Cells; D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005354:Fibrosarcoma / Q000098:blood supply / Q000188:drug therapy; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology
C117578:ANGPTL1 protein, human; D020533:Angiogenesis Inhibitors; D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins