Development of cancer therapeutic agents targeting choline transporter

• Project/Area Number: 22590248
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Tokyo Medical University
• Principal Investigator: INAZU Masato 東京医科大学, 医学部, 准教授 (00297269)
• Co-Investigator(Kenkyū-buntansha): TAJIMA Hirohisa 東京医科大学, 医学部, 助教 (50306833)
• Co-Investigator(Renkei-kenkyūsha): YAMADA Tomoko 東京医科大学, 医学部, 助手 (20468648)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: トランスポーター / コリン / 癌 / 細胞増殖 / 小細胞肺癌 / アポトーシス / 神経芽腫細胞 / アセチルコリン / フォスファチジルコリン

Research Abstract

Choline is essential for the synthesis of major membrane phospholipid phosphatidylcholine and neurotransmitter acetylcholine. Elevated levels of choline and up-regulated choline kinase activity have been detected in cancer cells. We found that choline transporter-like proteins (CTLs) are highly expressed in various cancer cells and are also involved in abnormal proliferation. Furthermore, the functional inhibition of CTLs could promote apoptotic cell death. Identification of this new CTLs-mediated choline transport system provides a potential new target for therapeutic intervention.

Research Products

• [Journal Article] Mutation of the Mg^(2+) Transporter SLC41A1 Results in a Nephronophthisis-Like Phenotype. (2013)
  • Author(s): Hurd TW, Otto EA, Mishima E, Gee HY, Inoue H, Inazu M, Yamada H, Halbritter J, Seki G, Konishi M, Zhou W, Yamane T, Murakami S, Caridi G, Ghiggeri G, Abe T, Hildebrandt F
  • Journal Title: J Am Soc Nephrol. Volume: 24 Issue: 6 Pages: 967-977
  • DOI: 10.1681/asn.2012101034
  • Peer Reviewed
• [Journal Article] Functional analysis of choline transporter in pancreatic cancer cells (2013)
  • Author(s): Inazu M, Sasaki J, Moriyama M, Hosoya R, Tai R
  • Journal Title: Journal of Pharmacological Sciences Volume: 121 Pages: 198-198
• [Journal Article] Macrolide antibiotics block autophagy flux and sensitize to bortezomib via endoplasmic reticulum stress-mediated CHOP induction in myeloma cells (2013)
  • Author(s): Moriya S, Che XF, Komatsu S, Abe A,Kawaguchi T, Gotoh A, Inazu M, Tomoda A, Miyazawa K
  • Journal Title: Int J Oncol Volume: 42 Issue: 5 Pages: 1541-1550
  • DOI: 10.3892/ijo.2013.1870
  • Peer Reviewed
• [Journal Article] Functional analysis of choline transporters in rheumatoid arthritis synovial fibroblasts (2012)
  • Author(s): Inazu M, Fujita S, Yamazaki T, Aratani S, Nakajima T, Nishioka K
  • Journal Title: Journal of Pharmacological Sciences Volume: 118 Pages: 208-208
• [Journal Article] Clarithromycin enhances bortezomib-induced cytotoxicity via endoplasmic reticulum stress-mediated CHOP (GADD153) induction and autophagy in breast cancer cells (2012)
  • Author(s): Komatsu S, Miyazawa K, Moriya S, Takase A, Naito M, Inazu M, Kohno N, ItohM, Tomoda A
  • Journal Title: Int J Oncol. Volume: 40 Issue: 4 Pages: 1029-1039
  • DOI: 10.3892/ijo.2011.1317
  • Peer Reviewed
• [Journal Article] Functional analysis of choline transporters in rheumatoid arthritis synovial fibroblasts. (2012)
  • Author(s): Masato Inazu
  • Journal Title: Journal of Pharmacological Sciences Volume: 118
• [Journal Article] Functional expression of cholinetransporter-like protein 1 (CTL1) in human neuroblastoma cells and its link to acetylcholine synthesis (2011)
  • Author(s): Yamada T, Inazu M, Tajima H, Matsumiya T
  • Journal Title: Neurochemistry International Volume: 58 Issue: 3 Pages: 354-365
  • DOI: 10.1016/j.neuint.2010.12.011
  • Peer Reviewed
• [Journal Article] Molecular and functional characterization of choline transporter in human leukemia cells. (2011)
  • Author(s): Inazu M, Fujita Y, Inuzuka M, Matsuoka M
  • Journal Title: Journal of Pharmacological Sciences Volume: 115 Pages: 178-178
  • Peer Reviewed
• [Journal Article] Molecular and functional characterization of choline transporter in human leukemia cells (2011)
  • Author(s): Masato Inazu
  • Journal Title: Journal of Pharmacological Sciences Volume: 115 Pages: 178-178
• [Journal Article] Functional expression of choline transporter-like protein 1 (CTL1) in human neuroblastoma cells and its link to acetylcholine synthesis (2011)
  • Author(s): Yamada T, Inazu M, Tajima H, Matsumiya T.
  • Journal Title: Neurochemistry International Volume: 58 Pages: 354-365
  • Peer Reviewed
• [Journal Article] Molecular and functional characterization of choline transporter in human leukemia cells (2011)
  • Author(s): Inazu M, Fujita Y, Inuzuka M, Matsuoka M.
  • Journal Title: Journal of Pharmacological Sciences Volume: 115 Pages: 178-178
• [Presentation] Functional analysis of choline transporter in pancreatic cancer cells (2013)
  • Author(s): Inazu M, Sasaki J, Moriyama M, Hosoya R, Tai R
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場(福岡県)
• [Presentation] Functional expression of choline transporter-like proteins in small cell lung carcinoma cells: A target molecule for lung cancer therapy. (2013)
  • Author(s): Inazu M, Yamada T, Kubota N, Yamanaka T, Tajima H
  • Organizer: 5th International Conference on Drug Discovery and Therapy.
  • Place of Presentation: Dubai (UAE).
• [Presentation] Functional expression of choline transporter-like proteins in small cell lung carcinoma cells: A target molecule for lung cancer therapy (2013)
  • Author(s): Masato Inazu
  • Organizer: 5th International Conference on Drug Discovery and Therapy
  • Place of Presentation: Dubai, UAE
• [Presentation] Functional analysis of choline transporter in pancreatic cancer cells (2013)
  • Author(s): Masato Inazu
  • Organizer: The 86th Annual Meeting of the Japanese Pharmacological Society
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] 膵癌細胞におけるコリントランスポーターの機能解析 (2012)
  • Author(s): 森山 充、佐々木 惇、細谷 龍作、戴黎、稲津 正人
  • Organizer: 第170回東京医科大学医学会総会
  • Place of Presentation: 東京医科大学病院(東京都)
  • Year and Date: 2012-11-17
• [Presentation] Mutation of the Renal Mg^<2+> Transporter SLC41A1 Causes a Nephronophthisis-like Phenotype (2012)
  • Author(s): Hurd T, Otto E, Inoue H, Yung Gee H, Inazu M, Konishi M, Ghiggeri G, Abe T and Hildebrandt F
  • Organizer: Kidney Week 2012
  • Place of Presentation: San Diego, CA
  • Year and Date: 2012-11-04
• [Presentation] コリントランスポーターは癌治療の標的分子である (2012)
  • Author(s): 稲津 正人、山田 朋子、田島 裕久
  • Organizer: 第7回トランスポーター研究会年会
  • Place of Presentation: 京都大学農学部(京都府)
  • Year and Date: 2012-06-09
• [Presentation] コリントランスポーターを標的とした癌治療薬の開発 (2012)
  • Author(s): 稲津 正人
  • Organizer: BIO tech 2012アカデミックフォーラム
  • Place of Presentation: 東京ビックサイト(東京都)
• [Presentation] コリントランスポーターを標的とした癌治療薬の開発 (2012)
  • Author(s): 稲津正人
  • Organizer: BIO tech 2012アカデミックフォーラム
  • Place of Presentation: 東京ビックサイト（東京都）
• [Presentation] コリントランスポーターは癌治療の標的分子である (2012)
  • Author(s): 稲津正人
  • Organizer: 第7回トランスポーター研究会年会
  • Place of Presentation: 京都大学農学部（京都府）
• [Presentation] 小細胞肺癌におけるcholine transporter-like protein 1とNa^<+>/H^<+>exchanger 1の機能的連関とアセチルコリン合成との関連性について (2011)
  • Author(s): 稲津 正人、山田 朋子、田島 裕久、松宮 輝彦、西岡 久寿樹
  • Organizer: 日光シンポジウム
  • Place of Presentation: 日光東照宮晃陽苑(栃木県)
  • Year and Date: 2011-12-17
• [Presentation] 小細胞肺癌におけるcholine transporter-like protein 1とNa+/H+ exchanger 1の機能的連関とアセチルコリン合成との関連性について (2011)
  • Author(s): 稲津正人、山田朋子、田島裕久、松宮輝彦、西岡久寿樹
  • Organizer: 日光シンポジウム
  • Place of Presentation: 日光東照宮晃陽苑(栃木県)
  • Year and Date: 2011-12-17
• [Presentation] 関節リウマチ滑膜繊維芽細胞におけるコリントランスポーターの機能解析 (2011)
  • Author(s): 藤井 翔太、山崎 友也、稲津 正人、荒谷 聡子、中島 利博、西岡 久寿樹
  • Organizer: 第168回東京医科大学医学会総会
  • Place of Presentation: 東京医科大学(東京都)
  • Year and Date: 2011-11-05
• [Presentation] ヒト神経芽腫細胞におけるcholine transporter-like proteinとNa^+/H^+exchangerの機能的連関とアセチルコリン合成との関連性について (2011)
  • Author(s): 稲津 正人、山田 朋子、田島 裕久、松宮 輝彦、西岡 久寿樹
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜パシフィコ(神奈川県)
  • Year and Date: 2011-09-15
• [Presentation] ヒト神経芽腫細胞におけるcholine transporter-like proteinとNa+/H+ exchangerの機能的連関とアセチルコリン合成との関連性について (2011)
  • Author(s): 稲津正人、山田朋子、田島裕久、松宮輝彦、西岡久寿樹
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜パシフィコ(神奈川県)
  • Year and Date: 2011-09-15
• [Presentation] 小細胞肺癌におけるコリントランスポーターの機能解析と癌治療への応用 (2011)
  • Author(s): 稲津 正人、西岡 久寿樹
  • Organizer: 第13回応用薬理シンポジウム
  • Place of Presentation: 千葉大学(千葉県)
  • Year and Date: 2011-09-04
• [Presentation] Functional expression of choline transporter-like protein 1 (CTL1) in human neuroblastoma cells and its link to acetylcholine synthesis. (2011)
  • Author(s): Inazu M, Yamada T, Tajima H, Matsumiya T, Nishioka K
  • Organizer: 8th IBRO World Congress of Neuroscience
  • Place of Presentation: Florence, Italy
  • Year and Date: 2011-07-16
• [Presentation] Functional expression of choline transporter-like protein 1 (CTL1) in human neuroblastoma cells and its link to acetylcholine synthesis (2011)
  • Author(s): Inazu M, Yamada T, Tajima H, Matsumiya T, Nishioka K
  • Organizer: 8th IBRO World Congress of Neuroscience
  • Place of Presentation: Florence, Italy
  • Year and Date: 2011-07-16
• [Presentation] Molecular and functional characterization of choline transporter in human leukemia cells (2011)
  • Author(s): Inazu M, Fujita Y, Inuzuka M, Matsuoka M
  • Organizer: The 84th Annual Meeting of the Japanese Pharmacological Society
  • Place of Presentation: 横浜パシフィコ(神奈川県)
  • Year and Date: 2011-03-23
• [Presentation] 大腸癌細胞におけるトランスポーターの機能解析および癌治療法の研究 (2010)
  • Author(s): 稲津 正人、黄司 博展、田島 裕久、山田 朋子、松宮 輝彦、西岡 久寿樹
  • Organizer: 第12回応用薬理シンポジウム
  • Place of Presentation: 横浜シンポジア(神奈川県)
  • Year and Date: 2010-09-19
• [Presentation] 膵癌細胞におけるコリントランスポーターの機能解析
  • Author(s): 稲津正人
  • Organizer: 第170回東京医科大学医学会総会
  • Place of Presentation: 東京医科大学病院（東京都）
• [Presentation] Mutation of the Renal Mg2+ Transporter SLC41A1 Causes a Nephronophthisis-like Phenotype
  • Author(s): Toby W. Hurd
  • Organizer: Kidney Week 2012
  • Place of Presentation: San Diego, CA
• [Patent(Industrial Property Rights)] 癌治療剤 (2011)
  • Inventor(s): 稲津正人、山田朋子、田島裕久
  • Industrial Property Rights Holder: 東京医科大学
  • Industrial Property Number: 2011-188053
  • Filing Date: 2011-08-30
• [Patent(Industrial Property Rights)] 癌治療剤 (2011)
  • Inventor(s): 稲津正人
  • Industrial Property Rights Holder: 東京医科大学
  • Industrial Property Number: 2011-188053
  • Filing Date: 2011-08-30