The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases

被引：166

作者：

Boucharaba, Ahmed

Serre, Claire-Marie

Guglielmi, Julien

Bordet, Jean-Claude

Clezardin, Philippe

Peyruchaud, Olivier ^{[1
]}

机构：

[1] INSERM, U664, F-69372 Lyon, France

[2] Univ Lyon 1, F-69008 Lyon, France

[3] Fac med Laennec, EA 3735, Lab Hemobiol, F-69008 Lyon, France

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2006年 / 103卷 / 25期

关键词：

breast cancer; platelet; treatment;

D O I：

10.1073/pnas.0600979103

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：

Platelet-derived lysophosphatidic acid (LPA) supports the progression of breast and ovarian cancer metastasis to bone. The mechanisms through which LPA promotes bone metastasis formation are, however, unknown. Here we report that silencing of the type 1 LPA receptor (LPA(1)) in cancer cells blocks the production of tumor-derived cytokines that are potent activators of osteoclast-mediated bone destruction and significantly reduces the progression of osteolytic bone metastases. Moreover, functional blockade of LPA action on its cognate receptor LPA(1) using a pharmacological antagonist mimics the effects of silencing LPA(1) in tumor cells in vitro and substantially reduces bone metastasis progression in animals. Overall, these results suggest that inhibition of platelet-derived LPA action on LPA, expressed by tumor cells may be a promising therapeutic target for patients with bone metastases.

引用

页码：9643 / 9648

页数：6

共 29 条

[1] Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid [J].