Involvement of LPA signaling via LPA receptor-2 in the promotion of malignant properties in osteosarcoma cells
- Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)
- Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)
- Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan)
Highlights: • LPA receptor expressions were changed by the long-term CDDP treatment in MG-63 cells. • The cell motile and invasive activities of MG-63 cells were stimulated by the long-term CDDP treatment. • LPAR2 expression was markedly elevated in highly migratory MG-63 cells. • Cellular functions induced by CDDP were suppressed by LPA{sub 2} knockdown. • LPA{sub 2} plays an important role in the acquisition of malignant properties during tumor progression in MG-63 cells. Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors mediates various biological effects in cancer cells. This study aimed to investigate the roles of LPA receptors in the regulation of cellular functions during tumor progression in osteosarcoma cells. Long-term cisplatin (CDDP)-treated MG63-C and MG63-R7-C cells were generated from osteosarcoma MG-63 and highly-migratory MG63-R7 cells, respectively. LPAR2 and LPAR3 expression levels were significantly higher in MG63-C cells than in MG-63 cells, while LPAR1 expression was reduced. MG63-C cells were highly motile, compared with MG-63 cells. MG63-C cell motility was suppressed by LPA{sub 2} knockdown and enhanced by the LPA{sub 1}/LPA{sub 3} antagonist, dioctanoylglycerol pyrophosphate. LPAR2 and LPAR3 expression levels were significantly elevated in MG63-R7-C cells in comparison with MG63-R7 cells. MG63-R7-C cells were found to be highly invasive, correlating with metalloproteinase-2 activation. MG63-R7-C cells formed large colonies, whereas colony formation was absent from MG63-R7 cells. Notably, MG63-R7-C cell activities were inhibited by LPA{sub 2} knockdown. These results suggest that LPA signaling via LPA{sub 2} plays an important role in the acquisition of malignant properties during tumor progression in MG-63 cells.
- OSTI ID:
- 23082675
- Journal Information:
- Experimental Cell Research, Vol. 369, Issue 2; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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