PHD2 in tumour angiogenesis.
Originally identified as the enzymes responsible for catalysing the oxidation of specific, conserved proline residues within hypoxia-inducible factor-1alpha (HIF-1alpha), the additional roles for the prolyl hydroxylase domain (PHD) proteins have remained elusive. Of the four identified PHD enzymes, PHD2 is considered to be the key oxygen sensor, as knockdown of PHD2 results in elevated HIF protein. Several recent studies have highlighted the importance of PHD2 in tumourigenesis. However, there is conflicting evidence as to the exact role of PHD2 in tumour angiogenesis. The divergence seems to be because of the contribution of stromal-derived PHD2, and in particular the involvement of endothelial cells, vs tumour-derived PHD2. This review summarises our current understanding of PHD2 and tumour angiogenesis, focusing on the influences of PHD2 on vascular normalisation and neovascularisation.
Chan
D A
DA
Department of Radiation Oncology, University of California, 2340 Sutter Street, S-332, Box 1331, San Francisco, CA 94143-1331, USA.
Giaccia
A J
AJ
D000818:Animals; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000209:etiology*; D011393:Procollagen-Proline Dioxygenase / Q000502:physiology*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases
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