Role of host proton-sensing receptors in tumorigenesis: analysis with receptor-deficient mice

• Project/Area Number: 23659029
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Gunma University
• Principal Investigator: OKAJIMA Fumikazu 群馬大学, 生体調節研究所, 教授 (30142748)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: プロトン感知性受容体 / TDAG8 / 細胞外 pH / 腫瘍 / マクロファージ / プロトン受容体 / がん

Research Abstract

It is well known that tumorigenesis is accompanied by extracellular acidification. However, the role of acidification remains unknown. Here, we investigated the role of recently identified proton-sensing receptors by using their receptor-deficient mice. Our results suggested that proton-sensing receptors are involved in tumorigenesis andextracellular acidification changes the M1-M2 macrophage phenotype.

Research Products

• [Journal Article] Ovarian cancer G-protein-coupled receptor 1 induces the expression of the pain mediator prostaglandin E2 in response to an acidic extracellular environment in human osteoblast-like cells (2012)
  • Author(s): Wang J, Sun Y, Tomura H, Okajima F.
  • Journal Title: Int J Biochem Cell Biol Volume: 44 Pages: 1937-1941
  • Peer Reviewed
• [Journal Article] Deficiency of Proton-Sensing Ovarian Cancer G Protein-Coupled Receptor 1Attenuates Glucose-Stimulated Insulin Secretion (2012)
  • Author(s): Nakakura T, Mogi C, Tobo M, Tomura H, Sato K, Kobayashi M, Ohnishi H, Tanaka S, Wayama M, Sugiyama T, Kitamura T, Harada A, and Okajima F.
  • Journal Title: Endocrinology Volume: 153 Pages: 4171-4180
  • Peer Reviewed
• [Journal Article] An orally active lysophosphatidic acid receptor antagonist attenuates pancreatic cancer invasionand metastasis in vivo (2012)
  • Author(s): Komachi M, Sato K, Tobo M, Mogi C, Yamada T, Ohta H, Tomura H, Kimura T, Im DS, Yanagida K, Ishii S, Takeyoshi I, and Okajima F.
  • Journal Title: Cancer Sci Volume: 103 Pages: 1099-1104
  • Peer Reviewed
• [Journal Article] An orally active lysophosphatidic acid receptor antagonist attenuates panereatic cancer invasion and metastasis in vivo (2012)
  • Author(s): Komachi M
  • Journal Title: Cancer Science Volume: (印刷中) Issue: 6 Pages: 1099-1104
  • DOI: 10.1111/j.1349-7006.2012.02246.x
  • Peer Reviewed
• [Journal Article] Deficiency of proton-sensing ovarian cancer G protein-coupled receptor 1 attenuates glucose- stimulated insulin secretion (2012)
  • Author(s): Nakakura T
  • Journal Title: Endocrinology Volume: 153 Issue: 9 Pages: 4171
  • DOI: 10.1210/en.2012-1164
  • Peer Reviewed
• [Journal Article] Ovarian cancer G-protein-coupled receptor 1 induces the expression of the pain mediator prostaglandin E2 in response to an acidic extracellular environment in human osteoblast-like cells (2012)
  • Author(s): Wang J, Sun Y, Tomura H, Okajima F.
  • Journal Title: Int J Biochem Cell Biol. Volume: 44 Issue: 11 Pages: 1937-1941
  • DOI: 10.1016/j.biocel.2012.07.015
  • Peer Reviewed
• [Journal Article] Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages (2011)
  • Author(s): He XD, Tobo M, Mogi C, Nakakura T, Komachi M, Murata N, Takano M, Tomura H, Sato K, Okajima F.
  • Journal Title: Biochem Biophys Res Commun Volume: 415 Pages: 627-631
  • Peer Reviewed
• [Journal Article] Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells (2011)
  • Author(s): Matsuzaki S, Ishizuka T, Yamada H, Kamide Y, Hisada T, Ichimonji I, Aoki H, Yatomi M, Komachi M, Tsurumaki H, Ono A, Koga Y, Dobashi K, Mogi C, Sato K, Tomura H, Mori M, and Okajima F.
  • Journal Title: Biochem Biophys Res Commun Volume: 413 Pages: 499-503
  • Peer Reviewed
• [Journal Article] Constitutively active heat shock factor 1 enhances glucose-driven insulinsecretion (2011)
  • Author(s): Uchiyama T, Tomono S, Utsugi T, Ohyama Y, Nakamura T, Tomura H, Kawazu S, Okajima F, and Kurabayashi M.
  • Journal Title: Metabolism Volume: 60 Pages: 789-798
  • Peer Reviewed
• [Journal Article] Unmasking of LPA(1) receptor-mediated migration response to lysophosphatidic acid by interleukin-1β-induced attenuation of Rho signaling pathways in ratastrocytes. (2011)
  • Author(s): Sato K, Horiuchi Y, Jin Y, Malchinkhuu E, Komachi M, Kondo T, Okajima F.
  • Journal Title: J Neurochem Volume: 117 Pages: 164-174
  • Peer Reviewed
• [Journal Article] Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages (2011)
  • Author(s): Xiao-Dong He
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 415 Issue: 4 Pages: 627
  • DOI: 10.1016/j.bbrc.2011.10.122
  • Peer Reviewed
• [Journal Article] Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth musele cells (2011)
  • Author(s): Matsuzaki S
  • Journal Title: Biochem Biophys Res Commun Volume: 413 Issue: 4 Pages: 499-503
  • DOI: 10.1016/j.bbrc.2011.08.087
  • Peer Reviewed
• [Journal Article] Constitutively active heat shock factor 1 enhances glucose-driven insulin secretion (2011)
  • Author(s): Uchiyama T
  • Journal Title: Metabolism Volume: 60 Issue: 6 Pages: 789-798
  • DOI: 10.1016/j.metabol.2010.07.029
  • Peer Reviewed
• [Journal Article] Unmasking of LPA(1)receptor-mediated migration response to lysophosphatidic acid by interleukin-1β-induced attenuation of Rho signaling pathways in rat astrocytes (2011)
  • Author(s): Sato K
  • Journal Title: J Neurochem Volume: 117 Issue: 1 Pages: 164-174
  • DOI: 10.1111/j.1471-4159.2011.07188.x
  • Peer Reviewed
• [Presentation] N1E115神経細胞における細胞外酸性pHによる細胞内Ca2+動員、Aktリン酸化とプロトン感知性受容体の関与 (2012)
  • Author(s): 佐藤幸市、小竹美絵、岡島史和
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡)
• [Presentation] Involvement of TDAG8 in extracellular acidification-induced inhibition of interleukin-1beta production in microglia (2012)
  • Author(s): Ye Jin, Koichi Sato, Fumikazu Okajima
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡)
• [Presentation] 膵β細胞におけるプロトン感知性OGR1を介したインスリン分泌シグナルの解析 (2012)
  • Author(s): 中倉敬、茂木千尋、戸村秀明、岡島史和
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡)
• [Presentation] プロトン感知性OGR1ファミリ-GPCRとその機能 (2012)
  • Author(s): 岡島史和
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡)
• [Presentation] プロトン感知性Gタンパク質共役型受容体OGR1KOマウスにおける気管支喘息モデルの解析 (2012)
  • Author(s): 青木悠、茂木千尋、久田剛志、石塚全、上出庸介、鶴巻寛朗、土橋邦生、岡島史和、森昌朋
  • Organizer: 第62回日本アレルギー学会秋季学術大会
  • Place of Presentation: 大阪国際会議場(大阪)
• [Presentation] プロトンはマウス肥満細胞からのサイトカイン産生を調節する (2012)
  • Author(s): 上出庸介、石塚全、鶴巻寛朗、山下均、山田秀典、宇津木光克、小野昭浩、古賀康彦、久田剛志、土橋邦生、岡島史和、森昌朋
  • Organizer: 第62回日本アレルギー学会秋季学術大会
  • Place of Presentation: 大阪国際会議場(大阪)
• [Presentation] ヒト膵臓がん細胞の浸潤・転移に対する経口可能なリゾホスファチジン酸受容体アンタゴニストKi16198の抑制作用 (2012)
  • Author(s): 佐藤幸市、小町麻由美、当房雅之、茂木千尋、岡島史和
  • Organizer: 第54回日本脂質生化学会
  • Place of Presentation: 九州大学医学部百年講堂(福岡)
• [Presentation] プロトン感知性OGR1ファミリ－GPCRとその機能 (2012)
  • Author(s): 岡島史和
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Invited
• [Presentation] 膵β細胞におけるプロトン感知性OGR1を介したインスリン分泌シグナルの解析 (2012)
  • Author(s): 中倉敬
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場（福岡）
• [Presentation] Involvement of TDAG8 in extracellular acidification-induced inhibition of interleukin-1beta production in microglia (2012)
  • Author(s): Ye Jin
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場（福岡）
• [Presentation] N1E115神経細胞における細胞外酸性pHによる細胞内Ca2+動員、Aktリン酸化とプロトン感知性受容体の関与 (2012)
  • Author(s): 佐藤幸市
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場（福岡）
• [Presentation] OGR1ファミリ－GPCRによるプロトン感知機構とその機能 (2011)
  • Author(s): 岡島史和
  • Organizer: 第84回日本生化学会大会(招待講演)
  • Place of Presentation: 国立京都国際会館（京都）
• [Remarks]
  • URL: http://www.imcr.gunma-u.ac.jp/lab/sigtra/
• [Remarks]
  • URL: http://imcr.showa.gunma-u.ac.jp/lab/signal/index.html