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0008-5472.CAN-20-4245.pdf | 1.14 MB | Adobe PDF | 見る/開く |
タイトル: | Intravital imaging identifies the VEGF-TXA₂ axis as a critical promoter of PGE₂ secretion from tumor cells and immune evasion |
著者: | Konishi, Yoshinobu Ichise, Hiroshi Watabe, Tetsuya Oki, Choji Tsukiji, Shinya Hamazaki, Yoko Murakawa, Yasuhiro https://orcid.org/0000-0002-5415-1352 (unconfirmed) Takaori-Kondo, Akifumi Terai, Kenta https://orcid.org/0000-0001-7638-3720 (unconfirmed) Matsuda, Michiyuki https://orcid.org/0000-0002-5876-9969 (unconfirmed) |
著者名の別形: | 小西, 義延 一瀬, 大志 渡部, 哲也 沖, 超二 築地, 真也 濱崎, 洋子 村川, 泰裕 高折, 晃史 寺井, 健太 松田, 道行 |
発行日: | Aug-2021 |
出版者: | American Association for Cancer Research (AACR) |
誌名: | Cancer Research |
巻: | 81 |
号: | 15 |
開始ページ: | 4124 |
終了ページ: | 4132 |
抄録: | Prostaglandin E₂ (PGE₂) promotes tumor progression through evasion of anti-tumor immunity. In stark contrast to cyclooxygenase-dependent production of PGE₂, little is known whether or not PGE₂ secretion is regulated within tumor tissues. Here, we show that VEGF-dependent release of thromboxane A₂ (TXA₂) triggers Ca²⁺ transients in tumor cells, culminating in PGE₂ secretion and subsequent immune evasion in the early stages of tumorigenesis. Ca²⁺ transients caused cPLA2 activation and triggered the arachidonic acid cascade. Ca²⁺ transients were monitored as the surrogate marker of PGE₂ secretion. Intravital imaging of BrafV600E mouse melanoma cells revealed that the proportion of cells exhibiting Ca²⁺ transients is markedly higher in vivo than in vitro. The TXA₂ receptor was indispensable for the Ca²⁺ transients in vivo, high intra-tumoral PGE₂ concentration, and evasion of anti-tumor immunity. Notably, treatment with a vascular endothelial growth factor (VEGF) receptor antagonist and an anti-VEGF antibody rapidly suppressed Ca²⁺ transients and reduced TXA₂ and PGE₂ concentrations in tumor tissues. These results identify the VEGF-TXA₂ axis as a critical promoter of PGE₂-dependent tumor immune evasion, providing a molecular basis underlying the immunomodulatory effect of anti-VEGF therapies. |
記述: | がん細胞が免疫から逃れるメカニズムの解明 --がん細胞と血管内皮細胞との細胞間相互作用--. 京都大学プレスリリース. 2021-05-28. |
著作権等: | The full-text file will be made open to the public on 25 May 2022 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/264627 |
DOI(出版社版): | 10.1158/0008-5472.CAN-20-4245 |
PubMed ID: | 34035084 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2021-05-28 |
出現コレクション: | 学術雑誌掲載論文等 |
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