Hypoxia-Induced Lysyl Oxidase Is a Critical Mediator of Bone Marrow Cell Recruitment to Form the Premetastatic Niche

被引：959

作者：

Erler, Janine T. ^{[1
,2
]}

Bennewith, Kevin L. ^{[1
,3
]}

Cox, Thomas R. ^{[2
]}

Lang, Georgina ^{[2
]}

Bird, Demelza ^{[2
]}

Koong, Albert ^{[1
]}

Le, Quynh-Thu ^{[1
]}

Giaccia, Amato J. ^{[1
]}

机构：

[1] Stanford Univ, Dept Radiat Oncol, Sch Med, Stanford, CA 94305 USA

[2] Inst Canc Res, Chester Beatty Labs, Sect Cell & Mol Biol, London SW3 6JB, England

[3] British Columbia Canc Res Ctr, Dept Med Biophys, Vancouver, BC V5Z 1L3, Canada

来源：

CANCER CELL | 2009年 / 15卷 / 01期

关键词：

MYELOID SUPPRESSOR-CELLS; TUMOR-BEARING HOST; IN-VITRO; IMMUNE SUPPRESSION; UP-REGULATION; IV-COLLAGEN; CANCER; METASTASIS; MACROPHAGES; INVASION;

D O I：

10.1016/j.ccr.2008.11.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor cell metastasis is facilitated by "premetastatic niches" formed in destination organs by invading bone marrow-derived cells (BMDCs). Lysyl oxidase (LOX) is critical for premetastatic niche formation. LOX secreted by hypoxic breast tumor cells accumulates at premetastatic sites, crosslinks collagen IV in the basement membrane, and is essential for CD11b+ myeloid cell recruitment. CD11b+ cells adhere to crosslinked collagen IV and produce matrix metalloproteinase-2, which cleaves collagen, enhancing the invasion and recruitment of BMDCs and metastasizing tumor cells. LOX inhibition prevents CD11b+ cell recruitment and metastatic growth. CD11b+ cells and LOX also colocalize in biopsies of human metastases. Our findings demonstrate a critical role for LOX in premetastatic niche formation and support targeting LOX for the treatment and prevention of metastatic disease.

引用

页码：35 / 44

页数：10

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