Inhibitory effects of lysophosphatidic acid receptor-5 on cellular functions of sarcoma cells

Abstract

Lysophosphatidic acid (LPA) is a bioactive lipid that interacts with G protein-coupled LPA receptors (LPA receptor-1 (LPA₁) to LPA₆). Here, we investigated the effects of LPA signaling via LPA₅ on cellular functions of sarcoma cells by generating Lpar5 overexpressing and Lpar5 knockdown cells from rat osteosarcoma and malignant fibrous histiocytoma cells, respectively. The cell motility activity of Lpar5 overexpressing cells was significantly lower, while Lpar5 knockdown cells showed high cell motility, compared with respective controls. Gelatin zymography showed that LPA₅ suppressed the activation of matrix metalloproteinase-2. LPA₅ also inhibited the cell motility activity of endothelial cells, correlating with the expression levels of vascular endothelial growth factor genes. These results suggest that LPA signaling via LPA₅ negatively regulates the cellular functions of rat sarcoma cells.

• Lysophosphatidic acid
• LPA receptor-5
• malignant fibrous histiocytoma
• osteosarcoma
• tumor progression

Acknowledgements

This study was supported in part by a Grant-in-Aid (24590493) for Scientific Research (C) from Japan Society for the Promotion of Science, and by Grants from the Ministry of Health, Labor and Welfare of Japan. The authors wish to express their gratitude to Dr G.W. Wolf for correction of the English and careful reading of the manuscript.