Journal
CANCER CELL
Volume 15, Issue 6, Pages 527-538Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2009.04.010
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Funding
- Silicon Valley Community Fellowship
- National Institutes of Health [NCI-CA-123823, NCI-CA-116685, NCI-CA-67166, CA-125618]
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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-kappa B-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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