Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone

被引：45

作者：

Hirbe, Angela C.

Rubin, Jessica

Uluckan, Ozge

Morgan, Elizabeth A.

Eagleton, Mark C.

Prior, Julie L.

Piwnica-Worms, David

Weilbaecher, Katherine N.

机构：

[1] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Mol Biol & Pharmacol,Mol Imaging Ctr, St Louis, MO 63110 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2007年 / 104卷 / 35期

关键词：

bone metastasis; osteoclast;

D O I：

10.1073/pnas.0705203104

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 [理学]; 0710 [生物学]; 09 [农学];

摘要：

CXCR4 regulates hematopoietic and tumor cell homing to bone, but its role during osteoclast (OC) development is unknown. We investigated the role of CXCR4 in osteoclastogenesis and in a model of bone metastasis. Compared with controls, mice reconstituted with CXCR4 null hematopoietic cells exhibited elevated markers of bone resorption, increased OC perimeter along bone, and increased bone loss. CXCR4-/- OCs demonstrated accelerated differentiation and enhanced bone resorption in vitro. Furthermore, tumor growth specifically in bone was significantly increased in mice reconstituted with CXCR4-/- hematopoietic cells. Finally, enhancement of bone tumor growth in the absence of CXCR4 was abrogated with the OC inhibitor, zoledronic acid. These data demonstrate that disruption of CXCR4 enhances osteoclastogenesis and suggest that inhibition of CXCR4 may enhance established skeletal tumor burden by increasing OC activity.

引用

页码：14062 / 14067

页数：6

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