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Effects of LPA receptor-mediated signaling on the modulation of cellular functions of pancreatic cancer cells cultured in fibroblast supernatants under hypoxic conditions

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Abstract

The tumor microenvironment (TME) consists of various cell types, including fibroblasts. The TME plays a central role in the promotion of tumor progression. In the present study, we investigated whether lysophosphatidic acid (LPA) receptor-mediated signaling regulates cellular functions by the TME of pancreatic cancer PANC-1 cells. To obtain fibroblast 3T3 cell supernatants, 3T3 cells were cultured in 5% charcoal stripped FCS-DMEM for 48 h. LPAR2 and LPAR3 expression levels were elevated in PANC-1 cells cultured in 3T3 cell supernatants. While PANC-1 cell motility was decreased by 3T3 cell supernatants, the cell survival to cisplatin (CDDP) of PANC-1 cells was markedly enhanced. Moreover, the cell survival to CDDP of PANC-1 cells cultured in 3T3 cell supernatants was increased by GRI-977,143 (LPA2 agonist) and (2 S)-OMPT (LPA3 agonist). Since hypoxia is caused by the restriction of adequate vascular networks to deliver oxygen into solid tumors, PANC-1 cells were cultured in 3T3 cell supernatants at 1% O2 conditions. The cell survival to CDDP of PANC-1 cells cultured in 3T3 cell supernatants at 1% O2 was significantly elevated, correlating with LPAR2 and LPAR3 expressions. These results suggest that LPA signaling via LPA2 and LPA3 is involved in the promotion of malignant properties by the TME in PANC-1 cells.

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Acknowledgements

This research was supported by JSPS KAKENHI Grant Numbers JP18K07249, 21K07109.

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Authors and Affiliations

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

    Miwa Takai, Aya Okuda, Yuka Amano, Narumi Yashiro, Koki Hara, Mao Yamamoto & Toshifumi Tsujiuchi

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  1. Miwa Takai
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  2. Aya Okuda
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  3. Yuka Amano
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  4. Narumi Yashiro
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  5. Koki Hara
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  6. Mao Yamamoto
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  7. Toshifumi Tsujiuchi
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Contributions

M.T. carried out all experiments and analyzed the results. A.O., Y.A., N.Y., K.H. and M.Y. supported the cell culture studies. T.T. designed this study and wrote the manuscript. All authors have read and approved the final version of the manuscript.

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Correspondence to Toshifumi Tsujiuchi.

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Takai, M., Okuda, A., Amano, Y. et al. Effects of LPA receptor-mediated signaling on the modulation of cellular functions of pancreatic cancer cells cultured in fibroblast supernatants under hypoxic conditions. J Bioenerg Biomembr 55, 169–177 (2023). https://doi.org/10.1007/s10863-023-09969-4

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