Functional analysis of stem cell marker SSEA-4 in prostate cancer cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09581
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: University of the Ryukyus
• Principal Investigator: SUDA Tetsuji 琉球大学, 医学(系)研究科(研究院), 助教 (40423347)
• Co-Investigator(Kenkyū-buntansha): 齋藤 誠一 琉球大学, 医学(系)研究科(研究院), 教授 (80235043)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: SSEA-4 / ST3GAL2 / 前立腺癌

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.

Free Research Field

腫瘍生物学

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。