Expression and role of voltage-gated calcium channels in gastric cancer and cancer stem cells.
Project/Area Number |
20K09016
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
Shiozaki Atsushi 京都府立医科大学, 医学(系)研究科(研究院), 講師 (40568086)
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Co-Investigator(Kenkyū-buntansha) |
大辻 英吾 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20244600)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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Keywords | 胃癌 / 胃十二指腸外科学 / 癌幹細胞 / イオンチャネル |
Outline of Research at the Start |
近年、様々なイオン輸送体が癌細胞機能を制御することが知られている。本研究では、"癌幹細胞特異的に発現した電位依存性Ca2+チャネル(VGCC)の制御により、胃癌の進展が抑制できる" という実験仮説の検証を行う。その結果から、癌幹細胞内イオン濃度変化を介した新たな腫瘍形成メカニズムを解明し、VGCC阻害薬であるアムロジピンやベラパミルを応用した、胃癌に対する斬新な治療概念の構築を目指す。
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Outline of Final Research Achievements |
Cells exhibiting strong CD44 activity were isolated from MKN74 gastric cancer (GC) cells by cell sorting, and cancer stem cells (CSCs) were generated with the sphere formation assay. Microarray analysis revealed CACNA2D1 was upregulated in CSCs, and its inhibitor amlodipine effectively decreased the number of tumorspheres. An immunohistochemical analysis revealed a relationship between strong CACNA2D1 expression and a poor prognosis in GC patients. CACNA2D1 was overexpressed in MKN7 and HGC27 cells, and CACNA2D1 depletion with siRNA suppressed cell proliferation, cell cycle progression, and invasion/migration, and induced apoptosis. The results of the microarray analysis showed that the apoptosis signaling pathway was enhanced via p53, BAX, and caspase 3 in CACNA2D1-depleted cells. These results provide an insight into the role of CACNA2D1 as a biomarker, and that its specific inhibitor, amlodipine, has potential as a targeted therapeutic agent against GC.
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Academic Significance and Societal Importance of the Research Achievements |
CACNA2D1が胃癌幹細胞において高発現し、その阻害剤であるアムロジピンが癌幹細胞特異的に抑制効果を示すことを新たに見出した。アムロジピンは高血圧・狭心症治療薬として臨床で用いられている薬剤であり、その抗腫瘍効果を明らかにしたことの社会的意義は大きいと考えられる。また、CACNA2D1のアポトーシスシグナル伝達経路を介する新たな腫瘍進展制御機構や、予後因子としての意義を明らかにし、バイオマーカーや治療標的としての可能性を示した。
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Report
(4 results)
Research Products
(68 results)
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[Journal Article] ANO9 regulates PD-L2 expression and binding ability to PD-1 in gastric cancer.2021
Author(s)
Katsurahara K, Shiozaki A, Kosuga T, Shimizu H, Kudou M, Arita T, Konishi H, Komatsu S, Kubota T, Fujiwara H, Okamoto K, Kishimoto M, Konishi E, Otsuji E.
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Journal Title
Cancer Science
Volume: 112
Issue: 3
Pages: 1026-1037
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical safety and efficacy of neoadjuvant combination chemotherapy of tranilast in advanced esophageal squamous cell carcinoma: Phase I/II study (TNAC).2020
Author(s)
Shiozaki A, Kudou M, Fujiwara H, Konishi H, Shimizu H, Arita T, Kosuga T, Yamamoto Y, Morimura R, Ikoma H, Kuriu Y, Kubota T, Okamoto K, Otsuji E.
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Journal Title
Medicine
Volume: 99
Issue: 50
Pages: e23633-e23633
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] ANO9 Regulated Cell Cycle in Human Esophageal Squamous Cell Carcinoma.2020
Author(s)
Katsurahara K, Shiozaki A, Kosuga T, Kudou M, Shoda K, Arita T, Konishi H, Komatsu S, Kubota T, Fujiwara H, Okamoto K, Kishimoto M, Konishi E, Marunaka Y, Otsuji E.
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Journal Title
Ann Surg Oncol.
Volume: ー
Issue: 9
Pages: 3218-3230
DOI
Related Report
Peer Reviewed
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[Presentation] 大腸癌幹細胞の低浸透圧ショックへの抵抗性2022
Author(s)
加藤俊治, 塩崎敦, 工藤道弘, 清水浩紀, 小菅敏幸, 木内純, 大橋拓馬, 有田智洋, 山本有祐, 小西博貴, 森村玲, 栗生宜明, 生駒久視, 窪田健, 藤原斉, 岡本和真, 大辻英吾
Organizer
第 122 回日本外科学会定期学術集会
Related Report
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[Presentation] Amlodipine, voltage-gated Ca2+ channel inhibitor, suppressed the growth of cancer stem cells in hepatocellular carcinoma2022
Author(s)
Atsushi Shiozaki, Kento Kurashima, Michihiro Kudou, Hiroki Shimizu,Toshiyuki Kosuga, Takuma Ohashi, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Ryo Morimura, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Eigo Otsuji
Organizer
第81回日本癌学会学術総会
Related Report
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[Presentation] Tranilast and furosemide suppressed the growth of cancer stem cells in esophageal adenocarcinoma2022
Author(s)
Hiroyuki Inoue, Atsushi Shiozaki, Toshiyuki Kosuga, Hiroki Shimizu, Michihiro Kudou, Takuma Ohashi, Tomohiro Arita, Hirotaka Konishi, Ryo Morimura, Takeshi Kubota, Hitoshi Fujiwara, Eigo Otsuji
Organizer
第81回日本癌学会学術総会
Related Report
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[Presentation] Correlation between TRPV2 and PD-L1 expression in advanced gastric cancer and its clinical significance2022
Author(s)
Tomoyuki Fukami, Atsushi Shiozaki, Jun Kiuchi, Takuma Ohashi, Hiroki Shimizu, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Ryo Morimura, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Eigo Otsuji
Organizer
第81回日本癌学会学術総会
Related Report
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[Presentation] The function analysis and clinical significance of CACNA2D1 in human gastric cancer2022
Author(s)
Naosuke Nakamichi, Atsushi Shiozaki, Hiroyuki Inoue, Toshiyuki Kosuga, Hiroki Shimizu, Michihiro Kudou, Takuma Ohashi, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Eigo Otsuji
Organizer
第81回日本癌学会学術総会
Related Report
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[Presentation] Gastric cancer stem cells are suppressed by voltage-gated Ca2+ channel inhibitors2021
Author(s)
Atsushi Shiozaki, Keita Katsurahara, Toshiyuki Kosuga, Michihiro Kudou, Hiroki Shimizu, Takuma Ohashi, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Ryo Morimura, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Eigo Otsuji
Organizer
第80回日本癌学会学術総会
Related Report
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[Presentation] The expression and role of CACNA2D1 in human gastric cancer2021
Author(s)
Hiroyuki Inoue, Atsushi Shiozaki, Toshiyuki Kosuga, Hiroki Shimizu, Michihiro Kudou, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Ryo Morimura, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Eigo Otsuji
Organizer
第80回日本癌学会学術総会
Related Report
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[Presentation] Colorectal cancer stem cells have resistance to hypotonic shock2021
Author(s)
Shunji Kato, Atsushi Shiozaki, Hiroki Shimizu, Michihiro Kudou, Toshiyuki Kosuga, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Ryo Morimura, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Eigo Otsuji
Organizer
第80回日本癌学会学術総会
Related Report
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[Presentation] ATP1A1 regulates tumor progression and affects postoperative prognosis in human gastric cancer2021
Author(s)
Kei Nakamura, Atsushi Shiozaki, Michihiro Kudou, Hiroki Shimizu, Toshiyuki Kosuga, Tomohiro Arita, Yusuke Yamamoto, Hirotaka Konishi, Ryo Morimura, Yoshiaki Kuriu, Hisashi Ikoma, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Mitsuo Kishimoto, Eigo Otsuji
Organizer
第80回日本癌学会学術総会
Related Report
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