Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation

被引：371

作者：

Wong, Carmen Chak-Lui ^{[1
,2
]}

Gilkes, Daniele M. ^{[1
,2
]}

Zhang, Huafeng ^{[1
,3
,7
]}

Chen, Jasper ^{[1
,2
]}

Wei, Hong ^{[1
,2
]}

Chaturvedi, Pallavi ^{[1
,2
]}

Fraley, Stephanie I. ^{[4
]}

Wong, Chun-Ming ^{[5
,6
]}

Khoo, Ui-Soon ^{[6
]}

Ng, Irene Oi-Lin ^{[5
,6
]}

Wirtz, Denis ^{[4
]}

Semenza, Gregg L. ^{[1
,2
,3
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Vasc Program, Inst Cell Engn, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA

[5] Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Liver Res, Hong Kong, Hong Kong, Peoples R China

[6] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pathol, Hong Kong, Hong Kong, Peoples R China

[7] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 39期

基金：

美国国家卫生研究院;

关键词：

extracellular matrix; lung metastasis; LYSYL OXIDASES; CARCINOMA; FAMILY; GENE; LOX;

D O I：

10.1073/pnas.1113483108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Primary tumors facilitate metastasis by directing bone marrow-derived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOX-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment. Only a subset of LOX family members was expressed in any individual breast cancer, but HIF-1 was required for expression in each case. Knockdown of HIF-1 or hypoxia-induced LOX family members reduced collagen cross-linking, CD11b(+) BMDC recruitment, and metastasis formation in the lungs of mice after orthotopic transplantation of human breast cancer cells. Metastatic niche formation is an HIF-1-dependent event during breast cancer progression.

引用

页码：16369 / 16374

页数：6

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