Identification of slow-cycling colon cancer stem cells by single cell gene expression analysis of chemoresistant cells
| Project/Area Number |
20K16230
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Teikyo University (2022)
National Cancer Center Japan (2020-2021) |
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Principal Investigator |
Kanda Yusuke 帝京大学, 先端総合研究機構, 研究員 (80803949)
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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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 抗がん剤抵抗性 / 大腸がん / 休止型がん幹細胞 / シングルセル解析 |
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| Outline of Research at the Start |
白血病等では休止型がん幹細胞が抗がん剤抵抗性の要因であるとされるが、大腸がんにおいても同様の細胞が存在するかは不明である。申請者は、大腸がん患者由来オルガノイドに誘導型H2B-EGFPを導入する事で休止型細胞を同定する実験系を構築した。本系への抗がん剤処理後に残存した休止型細胞は、高い再増殖活性を示したため、休止型がん細胞は抗がん剤抵抗性を持つ事が示唆された。そこで本研究は、シングルセル解析により休止型がん細胞に特徴的な遺伝子群を特定する。次に、抗がん剤抵抗性を与える遺伝子を決定する。以上より、大腸がんの抗がん剤抵抗性を改善させる治療法を開発する上で、休止型がん幹細胞が標的となる事を提示する。
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| Outline of Final Research Achievements |
Recently, a small group of slow-cycling cancer cells has been reported to be resistant to anticancer drugs, but the presence of the population in colon cancer is unknown. To prove the existence of slow-cycling cancer stem cells in colon cancer, we introduced induced H2B-EGFP into organoids established from colon cancer patients. We found that H2B-EGFP-positive cells are chemoresistant and that signature genes of H2B-EGFP-positive cells. In vitro system for gene KO was established. Next, we examined the presence of dormant cancer cells in the xenograft tumor. Colon cancer organoids were transplanted into immunodeficient mice, and H2B-EGFP expression was induced for a certain period, followed by administration of Irinotecan. As a result, we found that H2B-EGFP-positive cancer cells remained.
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| Academic Significance and Societal Importance of the Research Achievements |
休止型がん幹細胞は、抗がん剤抵抗性の要因であると考えられている。本研究で得られた成果は、ヒト大腸がん組織内に休止型がん幹細胞を見出したものであり、今後、休止型大腸がん幹細胞を標的とした治療法の開発が期待される。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] NF-κB suppression synergizes with E7386, an inhibitor of CBP/β-catenin interaction, to block proliferation of patient-derived colon cancer spheroids.2022
Author(s)
Kanda Y, Ohata H, Miyazaki T, Sakai H, Mori Y, Shiokawa D, Yokoi A, Owa T, Ochiai A, *Okamoto K.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 586
Pages: 93-99
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Integrative analyses of gene expression and chemosensitivity of patient-derived ovarian cancer spheroids link G6PD-driven redox metabolism to cisplatin chemoresistance.2021
Author(s)
Yamawaki K, Mori Y Sakai H, Kanda Y, Shiokawa D, Ueda U, Ishiguro T, Yoshihara K, Nagasaka K, Onda T, Kato T, Kondo T, Enomoto T, *Okamoto K.
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Journal Title
Cancer Lett.
Volume: 521
Pages: 29-38
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Loss of the cystine/glutamate antiporter in melanoma abrogates tumor metastasis and dramatically increases survival rates of mice.2020
Author(s)
Sato M, Onuma K, Domon M, Hasegawa S, Suzuki A, Kusumi R, Hino R, Kakihara N Kanda Y, Osaki M, Hamada J, Bannai S, Feederle R, Buday K, Angeli JPF, Proneth B, Conrad M, Okada F, and Sato H.
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Journal Title
Int J Cancer
Volume: 147
Issue: 11
Pages: 3224-3235
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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