Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-39544
Falcón, B L; Hashizume, H; Koumoutsakos, P; Chou, J; Bready, J V; Coxon, A; Oliner, J D; McDonald, D M (2009). Contrasting actions of selective inhibitors of angiopoietin-1 and angiopoietin-2 on the normalization of tumor blood vessels. American Journal of Pathology, 175(5):2159-70.
Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) have complex actions in angiogenesis and vascular remodeling due to their effects on Tie2 receptor signaling. Ang2 blocks Ang1-mediated activation of Tie2 in endothelial cells under certain conditions but is a Tie2 receptor agonist in others. We examined the effects of selective inhibitors of Ang1 (mL4-3) or Ang2 (L1-7[N]), alone or in combination, on the vasculature of human Colo205 tumors in mice. The Ang2 inhibitor decreased the overall abundance of tumor blood vessels by reducing tumor growth and keeping vascular density constant. After inhibition of Ang2, tumor vessels had many features of normal blood vessels (normalization), as evidenced by junctional accumulation of vascular endothelial-cadherin, junctional adhesion molecule-A, and platelet/endothelial cell adhesion molecule-1 in endothelial cells, increased pericyte coverage, reduced endothelial sprouting, and remodeling into smaller, more uniform vessels. The Ang1 inhibitor by itself had little noticeable effect on the tumor vasculature. However, when administered with the Ang2 inhibitor, the Ang1 inhibitor prevented tumor vessel normalization, but not the reduction in tumor vascularity produced by the Ang2 inhibitor. These findings are consistent with a model whereby inhibition of Ang2 leads to normalization of tumor blood vessels by permitting the unopposed action of Ang1, but decreases tumor vascularity primarily by blocking Ang2 actions.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||Special Collections > SystemsX.ch|
Special Collections > SystemsX.ch > Research, Technology and Development Projects > WingX
|DDC:||570 Life sciences; biology|
|Deposited On:||26 Nov 2010 17:02|
|Last Modified:||27 Nov 2013 19:41|
|Free access at:||PubMed ID. An embargo period may apply.|
|Citations:||Web of Science®. Times Cited: 66|
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