Expression and activity of ion transporters in gastric cancer stem cells.
Project/Area Number |
18K08689
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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 |
Ito Hiroshi 京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (20732481)
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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)
塩崎 敦 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40568086)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥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 Final Research Achievements |
Cells strongly expressing CD44 were separated from MKN74 cells, a human gastric cancer cell line, using FACS, and cancer stem cells (CSCs) were identified based on tumorsphere formation. The gene expression profiles of CSCs were examined by microarray analysis, and the expression of several genes related to voltage-gated Ca2+ channels (VGCCs), including CACNA2D1 and CACNB4, were up-regulated. The CACNA2D1 inhibitor, Amlodipine, and the CACNB4 inhibitor, Verapamil, were more cytotoxic at a lower concentration in CSCs than in non-CSCs, and effectively decreased the number of tumorspheres. In a xenograft model in nude mice, the administration of Amlodipine or Verapamil with Cisplatin resulted in significantly smaller tumor volumes than those of Cisplatin alone. These results suggest that that VGCCs are involved in the maintenance of CSCs, and that their specific inhibitors, Amlodipine and Verapamil, have potential as a targeted therapeutic agent against gastric cancer.
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Academic Significance and Societal Importance of the Research Achievements |
電位依存性カルシウムチャネル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やベラパミル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、ベラパミルは抗不整脈として臨床で広く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。
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Report
(4 results)
Research Products
(55 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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[Journal Article] The expression and role of TRPV2 in esophageal squamous cell carcinoma.2019
Author(s)
Kudou M, Shiozaki A, Yamazato Y, Katsurahara K, Kosuga T, 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
Sci Rep.
Volume: 9
Issue: 1
Pages: 16055-16055
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effect of low temperature on the regulation of cell volume after hypotonic shock in gastric cancer cells.2019
Author(s)
Shiozaki A, Yamazato Y, Kosuga T, Kudou M, Shoda K, Arita T, Konishi H, Komatsu S, Kubota T, Fujiwara H, Okamoto K, Marunaka Y, Otsuji E.
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Journal Title
Int J Oncol.
Volume: 55
Pages: 905-914
DOI
Related Report
Peer Reviewed
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[Journal Article] LRRC8A Expression Influences Growth of Esophageal Squamous Cell Carcinoma.2019
Author(s)
Konishi T, 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
Am J Pathol.
Volume: 189
Issue: 10
Pages: 1973-1985
DOI
Related Report
Peer Reviewed
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[Journal Article] Anion exchanger 2 suppresses cellular movement and has prognostic significance in esophageal squamous cell carcinoma2018
Author(s)
Shiozaki A, Hikami S, Ichikawa D, Kosuga T, Shimizu H, Kudou M, Yamazato Y, Kobayashi T, 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
Oncotarget
Volume: 9
Issue: 40
Pages: 25993-26006
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Detection of fusion gene in cell-free DNA of a gastric synovial sarcoma.2018
Author(s)
Ogino S, Konishi H, Ichikawa D, Hamada J, Shoda K, Arita T, Komatsu S, Shiozaki A, Okamoto K, Yamazaki S, Yasukawa S, Konishi E, Otsuji E.
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Journal Title
World J Gastroenterol.
Volume: 24
Issue: 8
Pages: 949-956
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] High CD44 gastric cancer stem cells are suppressed by voltage gated Ca2+ channel blocker.2019
Author(s)
Keita Katsurahara, Atsushi Shiozaki, Michihiro Kudou, Katsutoshi Shoda, Tomohiro Arita, Toshiyuki Kosuga, Hirotaka Konishi, Ryo Morimura, Yasutoshi Murayama, Takeshi Kubota, Masayoshi Nakanishi, Hitoshi Fujiwara, Eigo Otsuji.
Organizer
第78回日本癌学会学術総会
Related Report
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[Presentation] The development of novel targeted therapies to over-expressed ion transporters in esophageal cancer stem cells.2019
Author(s)
Yoshihisa Matsumoto, Michihiro Kudou, Atsushi Shiozaki, Toshiyuki Kosuga, Ryo Morimura , Yasutoshi Murayama, Yoshiaki Kuriu , Hisashi Ikoma, Takeshi Kubota, Masayoshi Nakanishi, Hitoshi Fujiwara, Kazuma Okamoto, Eigo Otsuji.
Organizer
第78回日本癌学会学術総会
Related Report
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[Presentation] 食道癌幹細胞特異的に発現するion channelの同定と新規標的治療への応用2018
Author(s)
塩﨑敦, 工藤道弘, 藤原斉, 小西博貴, 庄田勝俊, 有田智洋, 小菅敏幸, 森村玲, 村山康利, 栗生宜明, 生駒久視, 窪田健, 中西正芳, 岡本和真, 大辻英吾
Organizer
JDDW2018(第16回日本消化器外科学会大会)
Related Report
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[Presentation] Functional analysis and prognostic value of sodium iodide symporter (NIS) in gastric cancer2018
Author(s)
Atsushi Shiozaki, Yosuke Ariyoshi, Toshiyuki Kosuga, Michihiro Kudou, Katsutoshi Shoda, Tomohiro Arita, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Yoshinori Marunaka, Eigo Otsuji
Organizer
第77回日本癌学会学術総会
Related Report