The expression and function of C2GnT1 in ovarian carcinoma cells

• Project/Area Number: 17K16841
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Shinshu University
• Principal Investigator: Yamada Yasushi 信州大学, 学術研究院医学系(医学部附属病院), 助教 (60646652)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: C2GnT1 / 卵巣癌 / O-グリカン鎖 / 遊走能 / 浸潤能 / Oグリカン鎖 / 明細胞癌 / 粘液性癌 / 婦人科腫瘍学

Outline of Final Research Achievements

In this study, we investigated the expression and function of core 2 β1-6 N-acetylglucosaminyl transferase 1 (C2GnT1), which forms a core 2 branched structure on O-glycan, in ovarian cancer.
Immunohistochemical staining revealed that the increased expression of C2GnT1 was observed in clear cell carcinoma and mucinous carcinoma, known as treatment-resistant types of ovarian carcinoma. The WST-1 assay demonstrated that the increased expression of C2GnT1 facilitates proliferation in several ovarian carcinoma cell lines. In addition, C2GnT1 accelerates the migration and invasion in several cell lines. These results suggest that C2GnT1 is involved in the elevation of malignant potential in ovarian carcinoma cells and is a promising molecule as a novel therapeutic target.

Academic Significance and Societal Importance of the Research Achievements

これまで行われてきた卵巣癌の発癌・進展のメカニズムに関する研究は遺伝子産物である蛋白を中心になされており、糖鎖に関する研究は非常に少ない。しかし、細胞表面の糖鎖は免疫応答などで細胞同士の相互作用や接着にも実際に深く関与をしている分子であり、その構造や発現の違いで細胞機能が異なることが考えられる。本研究ではO-グリカン鎖のcore2分枝構造を形成するC2GnT1に注目しており、形成される糖鎖の構造や機能が解明できれば、これまでの蛋白をターゲットとする分子標的治療とは異なる機序での新たな治療法開発の基盤を開拓する可能性があると考えられる。