Collagen Prolyl Hydroxylases Are Essential for Breast Cancer Metastasis

被引：248

作者：

Gilkes, Daniele M. ^{[1
,2
,8
]}

Chaturvedi, Pallavi ^{[1
,2
]}

Bajpai, Saumendra ^{[8
,9
]}

Wong, Carmen C. ^{[1
,2
]}

Wei, Hong ^{[1
,2
]}

Pitcairn, Stephen ^{[1
,2
]}

Hubbi, Maimon E. ^{[1
,2
]}

Wirtz, Denis ^{[8
,9
]}

Semenza, Gregg L. ^{[1
,2
,3
,4
,5
,6
,7
,8
]}

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 Pediat, Baltimore, MD 21205 USA

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

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

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

[7] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA

[8] Johns Hopkins Univ, Johns Hopkins Phys Sci Oncol Ctr, Baltimore, MD 21205 USA

[9] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21205 USA

来源：

CANCER RESEARCH | 2013年 / 73卷 / 11期

关键词：

HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; GENE-EXPRESSION; FACTOR-I; TUMOR MICROENVIRONMENT; MAMMARY-TUMORS; LYSYL OXIDASE; HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA; 4-HYDROXYLASE; PROGRESSION; PHENOTYPE;

D O I：

10.1158/0008-5472.CAN-12-3963

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The presence of hypoxia and fibrosis within the primary tumor are two major risk factors for metastasis of human breast cancer. In this study, we demonstrate that hypoxia-inducible factor 1 activates the transcription of genes encoding collagen prolyl hydroxylases that are critical for collagen deposition by breast cancer cells. We show that expression of collagen prolyl hydroxylases promotes cancer cell alignment along collagen fibers, resulting in enhanced invasion and metastasis to lymph nodes and lungs. Finally, we establish the prognostic significance of collagen prolyl hydroxylase mRNA expression in human breast cancer biopsies and show that ethyl 3,4-dihydroxybenzoate, a prolyl hydroxylase inhibitor, decreases tumor fibrosis and metastasis in a mouse model of breast cancer. (C) 2013 AACR.

引用

页码：3285 / 3296

页数：12

共 54 条

[1] Cloning of the human prolyl 4-hydroxylase alpha subunit isoform alpha(II) and characterization of the type II enzyme tetramer - The alpha(I) and alpha(II) subunits do not form a mixed alpha(I)alpha(II)beta(2) tetramer [J].