[PDF][PDF] Tumor vasculature is regulated by PHD2-mediated angiogenesis and bone marrow-derived cell recruitment

DA Chan, TLA Kawahara, PD Sutphin, HY Chang… - Cancer cell, 2009 - cell.com
DA Chan, TLA Kawahara, PD Sutphin, HY Chang, JT Chi, AJ Giaccia
Cancer cell, 2009cell.com
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-κB …
Summary
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-κB-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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