The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases
| Autor: | Jean-Claude Bordet, Ahmed Boucharaba, Olivier Peyruchaud, Julien Guglielmi, Philippe Clézardin, Claire-Marie Serre |
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| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Osteoclasts Bone Neoplasms Biology Metastasis chemistry.chemical_compound Mice Internal medicine Cell Line Tumor Lysophosphatidic acid medicine Gene silencing Animals Humans Neoplasm Metastasis Receptors Lysophosphatidic Acid Receptor Cell Proliferation Multidisciplinary Cell growth Bone metastasis Isoxazoles Biological Sciences medicine.disease Gene Expression Regulation Neoplastic Endocrinology chemistry Cancer cell Cancer research Disease Progression Cytokines lipids (amino acids peptides and proteins) Female biological phenomena cell phenomena and immunity Lysophospholipids Propionates Ovarian cancer |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 103(25) |
| ISSN: | 0027-8424 |
| Popis: | 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 1 expressed by tumor cells may be a promising therapeutic target for patients with bone metastases. |
| Databáze: | OpenAIRE |
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