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LPA signaling through LPA receptors regulates cellular functions of endothelial cells treated with anticancer drugs

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Abstract

Lysophosphatidic acid (LPA) signaling via LPA receptors provides a variety of cellular functions, including angiogenesis. In this study, to assess an involvement of LPA receptors in cell motile activities of endothelial cells during chemotherapy, F-2 cells were treated with cisplatin (CDDP) and doxorubicin (DOX) at a concentration of 0.01 μM every 24 h for at least 1 month. The treatment of CDDP and DOX inhibited the expression levels of the LPA receptor-1 (Lpar1), Lpar2, and Lpar3 genes in F-2 cells. The cell motile activities of CDDP and DOX treated cells were relatively lower than those of untreated cells. Next, we investigated whether cancer cells could stimulate the cell motile activities of F-2 cells treated with CDDP and DOX. For cell motility assay, CDDP- and DOX-treated cells were co-cultured with pancreatic cancer PANC-1 cells. The cell motile activities of CDDP- and DOX-treated cells were significantly enhanced by the existence of PANC-1 cells, correlating with the LPA receptor expressions. In addition, the elevated cell motile activities were suppressed by the pretreatment of an autotaxin inhibitor S32826. These results suggest that LPA signaling via LPA receptors may regulate the cell motile activities of F-2 cells treated with anticancer drugs.

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References

  1. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186

    Article  CAS  PubMed  Google Scholar 

  2. Tozer GM, Kanthou C, Baguley BC (2005) Disrupting tumor blood vessels. Nat Rev Cancer 5:423–435

    Article  CAS  PubMed  Google Scholar 

  3. Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6:273–286

    Article  CAS  PubMed  Google Scholar 

  5. Bergers G, Hanahan D (2008) Modes of resistance to antiangiogenic therapy. Nat Rev Cancer 8:592–603

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62

    Article  CAS  PubMed  Google Scholar 

  7. Aikawa S, Hashimoto T, Kano K, Aoki J (2015) Lysophosphatidic acid as a lipid mediator with multiple biological actions. J Biochem 157:81–89

    Article  PubMed  Google Scholar 

  8. Ishii I, Fukushima N, Ye X, Chun J (2004) Lysophospholipid receptors: signaling and biology. Annu Rev Biochem 73:321–354

    Article  CAS  PubMed  Google Scholar 

  9. Lin M-E, Herr DR, Chun J (2010) Lysophosphatidic acid (LPA) receptors: signaling properties and disease relevance. Prostaglandins Other Lipid Mediat 91:130–138

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Tsujiuchi T, Araki M, Hirane M, Dong Y, Fukushima N (2014) Lysophosphatidic acid receptors in cancer pathobiology. Histol Histopathol 29:313–321

    CAS  PubMed  Google Scholar 

  11. Tsujiuchi T, Hirane M, Dong Y, Fukushima N (2014) Diverse effects of LPA receptors on cell motile activities of cancer cells. J Recept Signal Transduct 34:149–153

    Article  CAS  Google Scholar 

  12. Goetzl EJ, Dolezalova H, Kong Y, Hu Y-L, Jaffe RB, Kalli KR, Conover CA (1999) Distinctive expression and functions of the type 4 endothelial differentiation gene-encoded G protein-coupled receptor for lysophosphatidic acid in ovarian cancer. Cancer Res 59:5370–5375

    CAS  PubMed  Google Scholar 

  13. Hu Y-L, Tee M-K, Goetzl EJ, Auersperg N, Mills GB, Ferrara N, Jaffe RB (2001) Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. J Natl Cancer Inst 93:762–768

    Article  CAS  PubMed  Google Scholar 

  14. Fujita T, Miyamoto S, Onoyama I, Sonoda K, Mekada E, Nakano H (2003) Expression of lysophosphatidic acid receptors and vascular endothelial growth factor mediating lysophosphatidic acid in the development of human ovarian cancer. Cancer Lett 192:161–169

    Article  CAS  PubMed  Google Scholar 

  15. Yu S, Murph MM, Lu Y, Liu S, Hall HS, Liu J, Stephens C, Fang X, Mills GB (2008) Lysophosphatidic acid receptors determine tumorigenicity and aggressiveness of ovarian cancer cells. J Natl Cancer Inst 100:1630–1642

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Kitayoshi M, Kato K, Tanabe E, Yoshikawa K, Fukui R, Fukushima N, Tsujiuchi T (2012) Enhancement of endothelial cell migration by constitutively active LPA1-expressing tumor cells. Biochem Biophys Res Commun 422:339–343

    Article  CAS  PubMed  Google Scholar 

  17. Okabe K, Kato K, Teranishi M, Okumura M, Fukui R, Mori T, Fukushima N, Tsujiuchi T (2011) Induction of lysophosphatidic acid receptor-3 by 12-O-tetradecanoylphorbol-13-acetate stimulates cell migration of rat liver cells. Cancer Lett 309:236–242

    Article  CAS  PubMed  Google Scholar 

  18. Inoue S, Tanabe E, Shibata A, Hirane M, Araki M, Dong Y, Fukushima N, Tsujiuchi T (2013) Ethionine regulates cell motile activity through LPA receptor-3 in liver epithelial WB-F344 cells. Mol Cell Biochem 383:173–177

    Article  CAS  PubMed  Google Scholar 

  19. Tanabe E, Shibata A, Inoue S, Kitayoshi M, Fukushima N, Tsujiuchi T (2012) Regulation of cell motile activity through the different induction of LPA receptors by estrogens in liver epithelial WB-F344 cells. Biochem Biophys Res Commun 428:105–109

    Article  CAS  PubMed  Google Scholar 

  20. Shano S, Hatanaka K, Ninose S, Moriyama R, Tsujiuchi T, Fukushima N (2008) A Lysophosphatidic acid receptor lacking the PDZ-binding domain is constitutively active and stimulates cell proliferation. Biochim Biophys Acta 1783:748–759

    Article  CAS  PubMed  Google Scholar 

  21. Barbayianni E, Magrioti V, Moutevelis-Minakakis P, Kokotos G (2013) Autotaxin inhibitors: a patent review. Expert Opin Ther Pat 23:1123–1132

    Article  CAS  PubMed  Google Scholar 

  22. Aoki J, Inoue A, Okudaira S (2008) Two pathway for lysophosphatidic acid production. Biochim Biophys Acta 1781:513–518

    Article  CAS  PubMed  Google Scholar 

  23. Hayashi M, Okabe K, Kato K, Okumura M, Fukui R, Fukushima N, Tsujiuchi T (2012) Differential function of lysophosphatidic acid receptors in cell proliferation and migration of neuroblastoma cells. Cancer Lett 316:91–96

    Article  CAS  PubMed  Google Scholar 

  24. Samadi N, Bekele R, Capatos D, Venkatraman G, Sariahmetoglu M, Brindley DN (2011) Regulation of lysophosphatidate signaling by autotaxin and lipid phosphate phosphatases with respect to tumor progression, angiogenesis, metastasis and chemo-resistance. Biochimie 93:61–70

    Article  CAS  PubMed  Google Scholar 

  25. Brindley DN, Lin F-T, Tigyi GJ (2013) Role of the autotaxin-lysophosphatidate axis in cancer resistance to chemotherapy and radiotherapy. Biochim Biophys Acta 1831:74–85

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Panupinthu N, Lee HY, Mills GB (2010) Lysophosphatidic acid production and action: critical new players in breast cancer initiation and progression. Br J Cancer 102:941–946

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Shida D, Kitayama J, Yanaguchi H, Okaji Y, Tsuno NH, Watanabe T, Takuwa Y, Nagawa H (2003) Lysophosphatidic acid (LPA) enhances the metastatic potential of human colon carcinoma DLD1 cells through LPA1. Cancer Res 63:1706–1711

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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

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    Authors and Affiliations

    1. Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, Japan

      Shiori Mori, Mutsumi Araki, Shuhei Ishii, Miku Hirane, Kaori Fukushima, Ayaka Tomimatsu, Kaede Takahashi & Toshifumi Tsujiuchi

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

      Nobuyuki Fukushima

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    1. Shiori Mori
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    2. Mutsumi Araki
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    3. Shuhei Ishii
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    Correspondence to Toshifumi Tsujiuchi.

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    Shiori Mori and Mutsumi Araki have contributed equally to this work.

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    Mori, S., Araki, M., Ishii, S. et al. LPA signaling through LPA receptors regulates cellular functions of endothelial cells treated with anticancer drugs. Mol Cell Biochem 408, 147–154 (2015). https://doi.org/10.1007/s11010-015-2490-3

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    • DOI: https://doi.org/10.1007/s11010-015-2490-3

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