Title: Endothelial oxygen sensors regulate tumor vessel abnormalization by instructing phalanx endothelial cells
Authors: De Bock, Katrien
De Smet, Frederik
Leite-de-Oliveira, Rodrigo
Anthonis, Kristof
Carmeliet, Peter # ×
Issue Date: Jun-2009
Publisher: Springer
Series Title: Journal of Molecular Medicine vol:87 issue:6 pages:561-569
Abstract: An ancestral function of vessels is to conduct blood flow and supply oxygen (O(2)). In hypoxia, cells secrete angiogenic factors to initiate vessel sprouting. Angiogenic factors are balanced off by inhibitors, ensuring that vessels form optimally and supply sufficient oxygen (O(2)). By contrast, in tumors, excessive production of angiogenic factors induces vessels and their endothelial cell (EC) layer to become highly abnormal, thereby impairing tumor perfusion and oxygenation. In such pathological conditions, angiogenic factors act as "abnormalization factors" and promote the vessel "abnormalization switch." Recent genetic data indicate that ECs sense an imbalance in oxygen levels, by using the oxygen-sensing prolyl hydroxylase PHD2. In conditions of O(2) shortage, a decrease in PHD2 activity in ECs initiates a feedback that restores their shape, not their numbers. This induces ECs to align in a streamlined "phalanx" of tightly apposed, regularly ordered cobblestone ECs, which improves perfusion and oxygenation. As a result, EC normalization in PHD2 haplodeficient tumor vessels improves oxygenation and renders tumor cells less invasive and metastatic. This review discusses the role of PHD2 in the regulation of vessel (ab)normalization and the therapeutic potential of PHD2 inhibition for tumor invasiveness and metastasis.
ISSN: 0946-2716
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Switch Laboratory
Laboratory of Tumor Inflammation and Angiogenesis (Vesalius Research Center) (+)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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