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Lysophosphatidic acid receptor-2 (LPA 2) and LPA 5 regulate cellular functions during tumor progression in fibrosarcoma HT1080 cells

Kaede Takahashi, Kanako Minami, Shiho Otagaki, Kaichi Ishimoto, Kaori Fukushima, Nobuyuki Fukushima, Kanya Honoki, Toshifumi Tsujiuchi

Biochem Biophys Res Commun. 2018 Sep 18;503(4):2698-2703.

PMID: 30093116

Abstract:

Lysophosphatidic acid (LPA) receptors (LPA1 to LPA6) regulate a variety of malignant properties in cancer cells. In the present study, we investigated the roles of LPA receptors in the promotion of cellular functions during tumor progression in fibrosarcoma cells. To obtain long-term anticancer drug treated cells, human fibrosarcoma HT1080 cells were treated with methotrexate (MTX) and cisplatin (CDDP) for 6 months. LPAR2 and LPAR5 expressions were significantly higher in MTX-treated (HT-MTX) cells than in HT1080 cells. The cell motile and invasive activities of HT-MTX cells were significantly elevated compared with HT1080 cells. Although LPAR5 expression was increased in MTX and CDDP treated (HT-M-C) cells, no change of LPAR2 expression was observed. The cell motile and invasive activities of HT-M-C cells were lower than those of HT1080 cells. Moreover, to evaluate whether LPA receptors promote cell invasive activity, highly invasion (HT1080-M6) cells were established from HT1080 cells. The cell invasive activity of HT1080-M6 cells was approximately 4.5 times higher than HT1080 cell invasion. LPAR2 expression was markedly elevated in HT1080-M6 cells compared with HT1080 cells. The high cell invasion activity of HT1080-M6 cells was significantly suppressed by an antagonist of LPA2, H2L5186303. These results suggest that LPA2 acts as a key regulator of malignant properties in HT1080 cells.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP139262763 H2L5186303 H2L5186303 139262-76-3 Price
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