We addressed the effect of angiopoietin expression on tumor growth and meta
stasis. Overexpression of angiopoietin-2 (Ang-2) in Lewis lung carcinoma an
d TA3 mammary carcinoma cells inhibited their ability to form metastatic tu
mors and prolonged the survival of mice injected with the corresponding tra
nsfectants. In contrast, angiopoietin-1 (Ang-l) overexpression had no detec
table effect on the ability of either tumor type to disseminate. Tumors der
ived from Ang-2-overexpressing cells displayed aberrant angiogenic vessels
that took the form of vascular cords or aggregated vascular endothelial cel
ls with few associated smooth muscle cells. These vascular cords or aggrega
tes were accompanied by endothelial and tumor cell apoptosis, suggesting th
at an imbalance in Ang-2 expression with respect to Ang-1 and vascular endo
thelial growth factor may disrupt angiogenesis and tumor survival in vivo.
Our observations suggest that Ang-2 may play an important role in regulatin
g tumor angiogenesis.