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Cancer Cell. 2009 Jun 2;15(6):527-38. doi: 10.1016/j.ccr.2009.04.010.

Tumor vasculature is regulated by PHD2-mediated angiogenesis and bone marrow-derived cell recruitment.

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  • 1Center for Clinical Sciences Research, Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.


Sustained angiogenesis, through either local sprouting (angiogenesis) or the recruitment of bone marrow-derived cells (BMDCs) (vasculogenesis), is essential to the development of a tumor. How BMDCs are recruited to the tumor and their contribution to the tumor vasculature is poorly understood. Here, we demonstrate that both IL-8 and angiogenin contribute to the complementary pathways of angiogenesis and BMDC mobilization to increase tumor growth. These two factors are regulated by PHD2 in a HIF-independent but NF-kappaB-dependent manner. PHD2 levels are decreased in human cancers, compared with corresponding normal tissue, and correlate with an increase in mature blood vessels. Thus, PHD2 plays a critical role in regulating tumor angiogenesis.

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