Tumor Vasculature Is Regulated by PHD2-Mediated Angiogenesis and Bone Marrow-Derived Cell Recruitment

Denise A. Chan, Tiara L A Kawahara, Patrick D. Sutphin, Howard Y. Chang, Jen Tsan Chi, Amato J. Giaccia

Research output: Contribution to journalArticle

178 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)527-538
Number of pages12
JournalCancer Cell
Volume15
Issue number6
DOIs
StatePublished - Jun 2 2009

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Chan, D. A., Kawahara, T. L. A., Sutphin, P. D., Chang, H. Y., Chi, J. T., & Giaccia, A. J. (2009). Tumor Vasculature Is Regulated by PHD2-Mediated Angiogenesis and Bone Marrow-Derived Cell Recruitment. Cancer Cell, 15(6), 527-538. https://doi.org/10.1016/j.ccr.2009.04.010