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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-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.

Original publication

DOI

10.1016/j.ccr.2009.04.010

Type

Journal article

Journal

Cancer Cell

Publication Date

02/06/2009

Volume

15

Pages

527 - 538

Keywords

Animals, Basic Helix-Loop-Helix Transcription Factors, Bone Marrow Cells, Cells, Cultured, Endothelial Cells, Endothelium, Vascular, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Hypoxia-Inducible Factor-Proline Dioxygenases, Interleukin-8, Male, Mice, Mice, SCID, NF-kappa B, Neoplasm Transplantation, Neoplasms, Experimental, Neovascularization, Pathologic, Procollagen-Proline Dioxygenase, Ribonuclease, Pancreatic