Regulatory mechanism of cancer stem cell property using gastrointestinal cancer organoids and its clinical implication
Project/Area Number |
19H03443
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 49020:Human pathology-related
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Research Institution | Hiroshima University |
Principal Investigator |
Yasui Wataru 広島大学, 医系科学研究科(医), 名誉教授 (40191118)
|
Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | 消化管癌 / 癌幹細胞 / オルガノイド / 抗癌剤耐性 / KHDRBS3 / MYOF / 薬剤耐性 |
Outline of Research at the Start |
本研究では、消化管癌症例からオルガノイドを作成しTCGA等で提唱されているmolecular classificationを行なう。それぞれのmolecular subtypeごとに薬剤耐性オルガノイドを樹立し、parentalオルガノドとの間での遺伝子異常・遺伝子発現プロファイルを比較することにより、治療耐性(癌幹細胞)に特徴的な遺伝子・分子異常を同定する。同定した遺伝子・分子の細胞生物学的な機能解析により、治療耐性癌細胞性獲得とその維持のメカニズムを解明するとともに、その鍵となる遺伝子・分子異常の抗癌剤耐性マーカーとしての有用性を検討し、それを標的とする治療薬の開発を目指す。
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Outline of Final Research Achievements |
We established drug-resistant gastrointestinal cancer organoids (cancer stem cell organoids) having 5-FU resistance and L-OHP resistance. They were regarded as cancer stem cell-rich organoids in addition to drug resistance because of their tumorigenicity, metastatic potential, morphological changes, and CD44 expression. From the analysis of 5-FU-resistant and L-OHP-resistant organoids, KHDRBS3 and MYOF were found to regulate cancer stem cell properties, respectively. These findings will contribute to the application to the diagnosis and treatment for therapy-resistant cancer stem cells.
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Academic Significance and Societal Importance of the Research Achievements |
進行期の消化管癌では、外科的切除後の再発例や切除不能例に対する治療の中心は化学療法であるが、多くの場合は治療抵抗性を獲得し、最終的に患者は死に至る。治療耐性・治療後再発の大きな原因として癌幹細胞の存在が挙げられる。オルガノイド培養は三次元で器官様構造物をする作成する技術であり、幹細胞に富むことが知られている。本研究では、代表的な抗癌剤である5-FUとL-OHPに抵抗性のオルガノイドを樹立し、それを用いた解析によって癌幹細胞性を制御する遺伝子としてKHDRBS3とMYOFを同定した。これを標的とした新たな診断・治療の展開が期待される。
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Report
(4 results)
Research Products
(55 results)
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[Journal Article] Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance2021
Author(s)
Harada K, Sakamoto N, Ukai S, Yamamoto Y, Pham QT, Taniyama D, Honma R, Maruyama R, Takashima T, Ota H, Takemoto Y, Tanabe K, Ohdan H, Yasui W
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Journal Title
Gastric Cancer
Volume: 24
Issue: 6
Pages: 1264-1277
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] KHDRBS3 promotes multi-drug resistance and anchorage-independent growth in colorectal cancer.2021
Author(s)
Ukai S, Sakamoto N, Taniyama D, Harada K, Honma R, Maruyama R, Naka K, Hinoi T, Takakura Y, Shimizu W, Ohdan H, Yasui W
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Journal Title
Cancer Sci
Volume: 112
Issue: 3
Pages: 1196-1208
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impact of the ESM-1 Gene Expression on Outcomes in Stage II/III Gastric Cancer Patients Who Received Adjuvant S-1 Chemotherapy2020
Author(s)
Kano K, Sakamaki K, Oue N, Kimura Y, Hashimoto I, Hara K, Maezawa Y, Aoyama T, Fujikawa H, Hiroshima Y, Yamada T, Tamagawa H, Yamamoto N, Ogata T, Cho H, Ito H, Shiozawa M, Yukawa N, Yoshikawa T, Morinaga S, Rino Y, Yasui W, Masuda M, Miyagi Y, Oshima T.
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Journal Title
In vivo
Volume: 34
Issue: 1
Pages: 461-467
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] UC-63+ contributes to gastric cancer progression through regulation of NF-κB signaling2020
Author(s)
Sakamoto N, Sekino Y, Fukada, Pham QT, Honma R, Taniyama D, Ukai S, Takashima T, Hattori T, Naka K, Tanabe K, Ohdan H, Yasui W
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Journal Title
Gastric Cancer
Volume: 23
Issue: 5
Pages: 863-873
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] linical significance of glioma-associated oncogene 1 expression in patients with locally advanced gastric cancer administered adjuvant chemotherapy with S-1 after curative surgery2020
Author(s)
Hashimoto I, Oue N, Kimura Y, Hiroshima Y, Hara K, Maezawa Y, Kano K, Fujikawa H, Aoyama T, Numata M, Yamada T, Tamagawa H, Yamamoto N, Ogata T, Shiozawa M, Morinaga S, Rino Y, Yasui W, Masuda M, Miyagi Y, Oshima T
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Journal Title
Anticancer Res
Volume: 40
Issue: 10
Pages: 5815-5821
DOI
Related Report
Peer Reviewed
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[Journal Article] Molecular biological analysis of 5-FU-resistant gastric cancer organoids; KHDRBS3 contributes to the attainment of features of cancer stem cell2020
Author(s)
Ukai S, Honma R, Sakamoto N, Yamamoto Y, Pham QT, Harada K, Takashima T, Taniyama D, Asai R, Fukada K, Naka K, Tanabe K, Ohdan K, Yasui W
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Journal Title
Oncogene
Volume: 39
Issue: 50
Pages: 7265-7278
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] High gamma-glutamyl hydrolase and low folylpolyglutamate synthetase expression as prognostic biomarkers in patients with locally advanced gastric cancer who were administrated postoperative adjuvant chemotherapy with S-12020
Author(s)
Maezawa Y, Sakamaki K, Oue N, Kimura Y, Hashimoto I, Hara K, Kano K, Aoyama T, Hiroshima Y, Yamada T, Yamamoto N, Ogata T, Ito H, Cho H, Shiozawa M, Yoshikawa T, Morinaga S, Rino Y, Yausi W, Masuda M, Miyagi Y, Oshima T
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Journal Title
J Cancer Res Clin Oncol
Volume: 146
Issue: 1
Pages: 75-86
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Annexin A10 Is Involved in the Induction of Pancreatic Duodenal homeobox in Gastric Cancer Tissue, Cells and Organoids2020
Author(s)
Ishikawa A, Sakamoto N, Honma R, Taniyama D, Fukada K, Hattori T, Sentani K, Oue N, Yanagihara K, Tanabe K, Ohdan H, Yasui W.
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Journal Title
Oncol Rep
Volume: 43
Pages: 581-590
DOI
Related Report
Peer Reviewed
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[Journal Article] The clinicopathological significance of claspin in gastric cancer: Overexpression of claspin and its association with spheroid formation2019
Author(s)
Kobayashi G, Sentani K, Hattori T, Yamamoto Y, Imai T, Sakamoto N, Kuraoka K, OueN, Sasaki N, Taniyama K, Yasui W
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Journal Title
Human Pathology
Volume: 84
Pages: 8-17
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinicopathological significance of RCAN2 production in gastric carcinoma.2019
Author(s)
Hattori Y, Sentani K, Shinmei S, Oo HZ, Hattori T, Imai T, Sekino Y, Sakamoto N, Oue N, Niitsu H, Hinoi T, Ohdan H, Yasui W.
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Journal Title
Histopathology
Volume: 74
Issue: 3
Pages: 430-442
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Cancer Extracellular Vesicles Contribute to Stromal Heterogeneity by Inducing Chemokines in Cancer-Associated Fibroblasts2019
Author(s)
Naito Y, Yamamoto Y, Sakamoto N, Shimomura I, Kogure A, Kumazaki M, Yokoi A, Yashiro M, Kiyono T, Yanagihara K, Takahashi RU, Hirakawa K, Yasui W, Ochiya T.
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Journal Title
Oncogene
Volume: 38
Issue: 28
Pages: 5566-5579
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Synbiotics Suppress Colitis-Induced Tumorigenesis in a Colon-Specific Cancer Mouse Model2019
Author(s)
Saito Y, Hinoi T, Adachi T, Miguchi M, Niitsu H, Kochi M, Sada H, Sotomaru Y, Sakamoto N, Sentani K, Oue N, Yasui W, Tashiro H, Ohdan H.
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Journal Title
PLoS One
Volume: 14
Issue: 6
Pages: 0216393-0216393
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Targeting claudin-4 enhances CDDP-chemosensitivity of gastric cancer2019
Author(s)
Nishiguchi Y, Fujiwara-Tani R, Sasaki T, Luo Y, Ohmori H, Kishi S, Mori S, Goto K, Yasui W, Sho M*, Kuniyasu H
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Journal Title
Oncotarget
Volume: 10
Issue: 22
Pages: 2189-2202
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinical significance of KIAA1199 as a novel target for gastric cancer drug therapy2019
Author(s)
Oneyama M, Sakamoto N, Oue N, Kimura Y, Hiroshima Y, Hashimoto I, Hara K, Maezawa Y, Kano K, Aoyama T, Fujikawa H, Yamada T, Tamagawa H, Yamamoto N, Ogata T, Cho H, Ito H, Yukawa N, Shiozawa M, Yoshikawa T, Morinaga S, Rino Y, Masuda M, Miyagi Y, Yasui W, Oshima T
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Journal Title
Anticancer Res
Volume: 39
Issue: 12
Pages: 6567-6573
DOI
Related Report
Peer Reviewed
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[Presentation] Investigation on the role of MYOF in oxaliplatin-resistant gastric cancer organoids2022
Author(s)
Kenji Harada, Naoya Sakamoto, Shoichi Ukai, Quoc Thang Pham, Daiki Taniyama, Ririno Honma, Ryota Maruyama, Tsuyoshi Takashima, Kazuaki Tanabe, Hideki Ohdan, Wataru Yasui
Organizer
第94回 日本胃癌学会総会
Related Report
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[Presentation] Key role of myoferin in oxaliplatin-resistant gastric cancer organoids2021
Author(s)
Kenji Harada, Naoya Sakamoto, Shoichi Ukai, Quoc Thang Pham, Daiki Taniyama, Ririno Honma, Ryota Maruyama, Tsuyoshi Takashima, Kazuaki Tanabe, Hideki Ohdan, Wataru Yasui
Organizer
第80回 日本癌学会学術総会
Related Report
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