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

doi:10.1016/j.ccr.2009.04.010

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 journal › Article › peer-review

120 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 language	English (US)
Pages (from-to)	527-538
Number of pages	12
Journal	Cancer Cell
Volume	15
Issue number	6
DOIs	https://doi.org/10.1016/j.ccr.2009.04.010
State	Published - Jun 2 2009

Keywords

CELLCYCLE

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2009.04.010

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title = "Tumor Vasculature Is Regulated by PHD2-Mediated Angiogenesis and Bone Marrow-Derived Cell Recruitment",

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.",

keywords = "CELLCYCLE",

author = "Chan, {Denise A.} and Kawahara, {Tiara L A} and Sutphin, {Patrick D.} and Chang, {Howard Y.} and Chi, {Jen Tsan} and Giaccia, {Amato J.}",

note = "Funding Information: We kindly thank Drs. Duyen T. Dang and Long H. Dang (University of Michigan Comprehensive Cancer Center) for the generous gift of HIF-1 knockout cells, Dr. Andrew Keates for IL-8 reporter constructs, Dr. Giovanni Melillo and Pauline Chu for help with immunohistochemical analyses, and Dr. Trent A. Watkins for helpful discussions. This investigation was supported a Silicon Valley Community Fellowship, NCI-CA-123823 (D.A.C.), NCI-CA-116685, and NCI-CA-67166 (A.J.G), and CA-125618 awarded by the National Institutes of Health (J.T.C.). ",

year = "2009",

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doi = "10.1016/j.ccr.2009.04.010",

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T1 - Tumor Vasculature Is Regulated by PHD2-Mediated Angiogenesis and Bone Marrow-Derived Cell Recruitment

AU - Chan, Denise A.

AU - Kawahara, Tiara L A

AU - Sutphin, Patrick D.

AU - Chang, Howard Y.

AU - Chi, Jen Tsan

AU - Giaccia, Amato J.

N1 - Funding Information: We kindly thank Drs. Duyen T. Dang and Long H. Dang (University of Michigan Comprehensive Cancer Center) for the generous gift of HIF-1 knockout cells, Dr. Andrew Keates for IL-8 reporter constructs, Dr. Giovanni Melillo and Pauline Chu for help with immunohistochemical analyses, and Dr. Trent A. Watkins for helpful discussions. This investigation was supported a Silicon Valley Community Fellowship, NCI-CA-123823 (D.A.C.), NCI-CA-116685, and NCI-CA-67166 (A.J.G), and CA-125618 awarded by the National Institutes of Health (J.T.C.).

PY - 2009/6/2

Y1 - 2009/6/2

N2 - 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.

AB - 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.

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

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