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Enhanced cellular functions through induction of LPA2 by cisplatin in fibrosarcoma HT1080 cells

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Abstract

Lysophosphatidic acid (LPA) is a simple biophysical lipid which interacts with at least six subtypes of G protein-coupled LPA receptors (LPA1–LPA6). In cancer cells, LPA signaling via LPA receptors is involved in the regulation of malignant properties, such as cell growth, motility, and invasion. The aim of this study was to assess whether LPA receptors regulate cellular functions of fibrosarcoma cells treated with anticancer drug. HT1080 cells were maintained by the stepwise treatment of cisplatin (CDDP) at a range of 0.01 to 1.0 µM for approximately 6 months. The cell motile and invasive activities of long-term CDDP-treated (HT-CDDP) cells were significantly stimulated by LPA treatment, while HT-CDDP cells in the static state showed the low cell motile and invasive activities in comparison with HT1080 cells. Since the expression level of LPAR2 gene was markedly elevated in HT-CDDP cells, LPA2 knockdown cells were generated from HT-CDDP cells. The cell motile and invasive activities of HT-CDDP cells were reduced by LPA2 knockdown. In colony assay, large-sized colonies formed by long-term CDDP treatment were suppressed by LPA2 knockdown. In addition, LPA2 knockdown cells reduced LPA production by autotaxin (ATX), correlating with ATX expression level. These results suggest that LPA signaling via LPA2 may play an important role in the regulation of cellular functions in HT1080 cells treated with CDDP.

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Acknowledgements

This work was supported by JSPS KAKENHI Grant Number 24590493 and by Grants from the Faculty of Science and Engineering, Kindai University.

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Authors and Affiliations

  1. Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiōsaka, Osaka, 577-8502, Japan

    Kaede Takahashi, Kaori Fukushima & Toshifumi Tsujiuchi

  2. Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiōsaka, Osaka, 577-8502, Japan

    Nobuyuki Fukushima

  3. Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan

    Kanya Honoki

Authors
  1. Kaede Takahashi
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  2. Kaori Fukushima
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  3. Nobuyuki Fukushima
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  4. Kanya Honoki
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  5. Toshifumi Tsujiuchi
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Correspondence to Toshifumi Tsujiuchi.

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Takahashi, K., Fukushima, K., Fukushima, N. et al. Enhanced cellular functions through induction of LPA2 by cisplatin in fibrosarcoma HT1080 cells. Mol Cell Biochem 431, 29–35 (2017). https://doi.org/10.1007/s11010-017-2971-7

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  • DOI: https://doi.org/10.1007/s11010-017-2971-7

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