The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases
- 20 June 2006
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 103 (25) , 9643-9648
- https://doi.org/10.1073/pnas.0600979103
Abstract
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 (LPA1) 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 LPA1using a pharmacological antagonist mimics the effects of silencing LPA1in tumor cellsin vitroand substantially reduces bone metastasis progression in animals. Overall, these results suggest that inhibition of platelet-derived LPA action on LPA1expressed by tumor cells may be a promising therapeutic target for patients with bone metastases.Keywords
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