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

被引：237

作者：

Chan, Denise A. ^{[1
]}

Kawahara, Tiara L. A. ^{[2
]}

Sutphin, Patrick D. ^{[1
]}

Chang, Howard Y. ^{[2
]}

Chi, Jen-Tsan ^{[3
]}

Giaccia, Amato J. ^{[1
]}

机构：

[1] Stanford Univ, Ctr Clin Sci Res, Dept Radiat Oncol, Stanford, CA 94305 USA

[2] Stanford Univ, Programs Epithelial Biol & Canc Biol, Stanford, CA 94305 USA

[3] Duke Med Ctr, Inst Genome Sci & Policy, Dept Mol Genet & Microbiol, Durham, NC 27708 USA

来源：

CANCER CELL | 2009年 / 15卷 / 06期

基金：

美国国家卫生研究院;

关键词：

HYPOXIA-INDUCIBLE-FACTOR; PROLYL HYDROXYLASE PHD2; HIPPEL-LINDAU PROTEIN; TRANSCRIPTIONAL ACTIVITY; PROLINE HYDROXYLATION; PATHWAY SIGNATURES; BREAST-CANCER; HIF-ALPHA; HIF-1-ALPHA; GROWTH;

D O I：

10.1016/j.ccr.2009.04.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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-kappa B-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.

引用

页码：527 / 538

页数：12

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