Visualization of cancer-initiating cells and search for an effective treatment using gastric cancer organoids
Project/Area Number |
17K07161
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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 |
Research Field |
Tumor biology
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Research Institution | Kanazawa University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | がん幹細胞 / 胃がん / オルガノイド / LGR5 / 癌 / 再生医学 / 細胞・組織 / 発現制御 / 遺伝子 |
Outline of Final Research Achievements |
Our goal is to establish an effective treatment for gastric cancer. By using newly established mouse and human gastric cancer organoids, we tried to identify cancer-initiating cells and clarify the mechanism which induce their malignancy. Furthermore, based on knowledges, we searched for an effective treatment for gastric cancer in vivo. We proceeded our research with focusing on an epithelial stem cell marker, LGR5 and found that LGR5 positive gastric cancer cells could be the cancer-initiating cell. By a comprehensive gene expression analysis, we found a group of genes which could regulate proliferation and maintenance of cancer-initiating cells. We orthotopically transplanted genetically modified organoids into mouse stomach and found that some genes can regulate the metastatic ability of cancer-initiating cells. Furthermore, we found drug candidates which can selectively eliminate cancer-initiating cells.
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Academic Significance and Societal Importance of the Research Achievements |
胃がんは肺がんと並びがんによる死因の多くを占める。がんの再発と転移の背景には治療抵抗性を持つがん幹細胞の存在が示唆されており、がんの根絶に向けてがん幹細胞の増殖能・分化能を抑制しつつ、がん全体を標的とする治療法の確立が急務となっている。しかし、胃におけるがん幹細胞の正体は明らかになっておらず、そのため悪性度の高い胃がんに対する真に効果的な治療法の確立には至っていない。本研究では、胃がん幹細胞の同定と増殖性・可塑性・分化能を制御する機構の解明を通して、胃がんを根絶する真に効果的な治療法の確立へ貢献する。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Distinct Localization of Mature HGF from its Precursor Form in Developing and Repairing the Stomach.2019
Author(s)
Jangphattananont N, Sato H, Imamura R, Sakai K, Terakado Y, Murakami K, Barker N, Oshima H, Oshima M, Takagi J, Kato Y, Yano S, Matsumoto K
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Journal Title
International Journal of Molecular Sciences
Volume: 12
Issue: 12
Pages: 2955-2955
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Interleukin 1 Up-regulates MicroRNA 135b to Promote Inflammation-Associated Gastric Carcinogenesis in Mice.2018
Author(s)
Han TS, Voon DC, Oshima H, Nakayama M, Echizen K, Sakai E, Yong ZWE, Murakami K, Yu L, Minamoto T, Ock CY, Jenkins BJ, Kim SJ, Yang HK, Oshima M
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Journal Title
Interleukin 1 Up-regulates MicroRNA 135b to Promote Inflammation-Associated Gastric Carcinogenesis in Mice
Volume: 156
Issue: 4
Pages: 1140-1155
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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