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 e ndothelial cells leads to initiation of angiogenesis, We stably transfected HT29 colon cancer cells with cDNA constructs for Ang-1 or -2 or with vecto r alone, injected the cells s.c into nude mite, 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 mere larg er than the tumors produced in the other groups; those tumors also had high er vessel counts and proliferative indices than tumors in the other groups, Tumors produced by the Ang-1 transfectants had fewer vessels and lower tum or cell proliferative indices than tumors in the other groups. These data s uggest that imbalances between Ang-1 and -2 that result in a net gain of An g-2 activity lead to enhanced tumor angiogenesis and growth.