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

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

Open link

Publication date

June 2009

DOI

10.1016/j.ccr.2009.04.010

Publisher

Elsevier Inc.

Abstract

SummarySustained 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 angioge...