論文

査読有り
2021年8月19日

Sphingosine-1-Phosphate Induces ATP Release via Volume-Regulated Anion Channels in Breast Cell Lines

Life
  • Kishio Furuya
  • ,
  • Hiroaki Hirata
  • ,
  • Takeshi Kobayashi
  • ,
  • Masahiro Sokabe

11
8
開始ページ
851
終了ページ
851
記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/life11080851
出版者・発行元
MDPI AG

High interstitial level of ATP and its lysate adenosine in the cancer microenvironment are considered a halo mark of cancer. Adenosine acts as a strong immune suppressor. However, the source of ATP release is unclear. We clarified the release of ATP via volume-regulated anion channels (VRACs) in breast cell lines using an ATP luminescence imaging system. We detected a slowly rising diffuse pattern of ATP release that was only observed in undifferentiated cells, not in differentiated primary cultured cells. This was confirmed by suppression with DCPIB, a blocker of VRACs, and shRNA for LRRC8A, an indispensable subunit of VRACs. We herein demonstrated that the inflammatory mediator sphingosine-1-phosphate (S1P), which exists abundantly in the cancer microenvironment, induced a diffuse pattern of ATP release isovolumetrically. The response was dose-dependent and suppressed by the knock-down of LRRC8A. It was also suppressed by blockers of S1P receptor 1 and 2 (W146 and JTE013, respectively). RTqPCR demonstrated the prominent presence of S1PR1 and S1PR2 mRNAs. We discussed the roles of S1P-induced ATP release in the cancer microenvironment.

リンク情報
DOI
https://doi.org/10.3390/life11080851
URL
https://www.mdpi.com/2075-1729/11/8/851/pdf
ID情報
  • DOI : 10.3390/life11080851
  • eISSN : 2075-1729
  • ORCIDのPut Code : 98856295

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