Stabilization of breast cancer xenograft tumour neovasculature by angiopoietin-1.
Angiopoietin-1 is a promoter of physiological vasculogenesis and angiogenesis because it induces vascular branching and smooth muscle recruitment to newly formed blood vessels. However, angiopoietin-1 expression in tumours appears to be uncommon, and angiopoietin-1 overexpression in cancer cells has been reported to lead to inhibition of xenograft tumour growth. We report here that angiopoietin-1 overexpression resulted in stabilization of tumour edge-associated blood vessels, as it prevented vessel dilation and dissociation of smooth muscle cells from existing vessels. In addition, angiopoietin-1 stimulated an infiltration of mesenchymal cells into the tumours, such that the coverage of microvessels by pericytes increased markedly, and the cancer cells were separated into small masses by the host stroma. The rates of both cancer cell proliferation and apoptosis decreased significantly in the presence of angiopoietin-1. Tie2, the receptor for angiopoietin-1, was found to be present in vascular smooth muscle cells in culture in addition to endothelial cells. These findings suggest that a vascular stabilization effect of angiopoietin-1 accounts for the inhibition of tumour growth.
Tian
S
S
Department of Oncology, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington DC 20007, USA.
Hayes
A J
AJ
Metheny-Barlow
L J
LJ
Li
L-Y
LY
D042683:Angiopoietin-1; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000098:blood supply*; D002455:Cell Division / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D042787:Receptor, TIE-2; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014664:Vasodilation
D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D008562:Membrane Glycoproteins; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2