The effects of angiopoietin-1 and -2 on tumor growth and angiogenesis in human colon cancer.
Angiopoietin (Ang) 1 and Ang-2 are important regulators of endothelial cell survival. Current models suggest that an increase in Ang-2 expression in endothelial cells leads to initiation of angiogenesis. We stably transfected HT29 colon cancer cells with cDNA constructs for Ang-1 or -2 or with vector alone, injected the cells s.c. into nude mice, and assessed tumor growth. Immunohistochemical analyses confirmed sustained increases of Ang-1 and -2 in the tumors. The tumors produced by the Ang-2-transfected cells were larger than the tumors produced in the other groups; those tumors also had higher vessel counts and proliferative indices than tumors in the other groups. Tumors produced by the Ang-1 transfectants had fewer vessels and lower tumor cell proliferative indices than tumors in the other groups. These data suggest that imbalances between Ang-1 and -2 that result in a net gain of Ang-2 activity lead to enhanced tumor angiogenesis and growth.
Ahmad
S A
SA
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Liu
W
W
Jung
Y D
YD
Fan
F
F
Wilson
M
M
Reinmuth
N
N
Shaheen
R M
RM
Bucana
C D
CD
Ellis
L M
LM
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015152:Blotting, Northern; D002455:Cell Division / Q000502:physiology; D003110:Colonic Neoplasms / Q000098:blood supply / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D019073:HT29 Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014183:Transplantation, Heterologous
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467628:Angpt1 protein, mouse; D008562:Membrane Glycoproteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins