| Project/Area Number |
20K09581
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
SUDA Tetsuji 琉球大学, 医学(系)研究科(研究院), 助教 (40423347)
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| Co-Investigator(Kenkyū-buntansha) |
齋藤 誠一 琉球大学, 医学(系)研究科(研究院), 教授 (80235043)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | SSEA-4 / ST3GAL2 / 前立腺癌 / 上皮間葉転換 / 去勢抵抗性前立腺癌 / Drug resistance / Signaling pathway / ST3Gal2 / ST3Gal II |
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| Outline of Research at the Start |
発生初期の受精卵やES細胞では、未分化を示すマーカーの1つStage-specific embryonic antigen (SSEA-4)が発現している。近年、このSSEA-4は幾つかの癌においても発現し、難治癌の根幹であるがん幹細胞に似た特徴をもつことが示された。そこで本研究は、前立腺癌におけるSSEA-4の役割を明らかにし、癌の治療につなげていく
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| Outline of Final Research Achievements |
Stage-specific embryonic antigen-4 (SSEA-4), which was originally found in mouse early embryo, has been used as a marker for identification of stem cells. In recent years, SSEA-4 has been reported to be expressed in highly malignant solid cancer cells. SSEA-4 was also associated with anti-cancer drug resistance in breast cancer and osteosarcoma. In prostate cancer, we showed that SSEA-4 was linked to the malignant potential such as invasion and biochemical recurrence after radical prostatectomy. Moreover, expression of SSEA-4 was associated with hormone resistance and greatly enhanced in castration-resistant prostate cancer cells. To clarify the biological function of SSEA-4 in prostate cancer cells, we knocked out SSEA-4 synthase ST3GAL2 gene. We found that ST3GAL2 knockout caused expression changes of many genes involved in various signaling pathways and cancers etc., and phenotypically resistance to two anti-cancer drugs were decreased in ST3GAL2 knockout clones.
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| Academic Significance and Societal Importance of the Research Achievements |
SSEA-4は高悪性度の固形癌で発現し、抗がん剤耐性やホルモン療法耐性と関連する。我々が、前立腺癌細胞株において、SSEA-4合成酵素のST3GAL2遺伝子をノックアウトしたところ、ノックアウト細胞株では２種類の抗がん剤に対する耐性能の低下を示した。これはST3GAL2の制御により、抗がん剤を減量でき、少ない有害事象で同程度の抗腫瘍効果を発揮できる可能性がある。また、比較的長期に抗がん剤を使用できると考えられ、予後延長が期待できる。
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