Tumor vasculature is regulated by PHD2-mediated angiogenesis and bone marrow-derived cell recruitment.
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.
Chan
Denise A
DA
Center for Clinical Sciences Research, Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
Kawahara
Tiara L A
TL
Sutphin
Patrick D
PD
Chang
Howard Y
HY
Chi
Jen-Tsan
JT
Giaccia
Amato J
AJ
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001854:Bone Marrow Cells / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000378:metabolism; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011393:Procollagen-Proline Dioxygenase / Q000502:physiology*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D016209:Interleukin-8; D016328:NF-kappa B; D011393:Procollagen-Proline Dioxygenase; D012259:Ribonuclease, Pancreatic; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C490190:EGLN1 protein, human; C046366:angiogenin