Targeting ID2 expression reduces aggressiveness in human salivary gland cancer cells

• Project/Area Number: 18K09748
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Kyushu University
• Principal Investigator: Sumida Tomoki 九州大学, 歯学研究院, 共同研究員 (50314951)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 腺様嚢胞癌 / 浸潤 / 転移 / ID2分化抑制因子 / 浸潤、転移 / 口腔癌 / ID2

Outline of Final Research Achievements

ID2 knockdown triggers important changes in salivary gland cancer (SGC) cell behavior, that is, it significantly reduces the expression of c-myc and N-cadherin, induces p21, and E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. Moreover, ID2 knockdown suppresses the expression of matrix metalloproteinase 9. In conclusion, ID2 expression maintains an aggressive phenotype in SGC cells, and ID2 repression triggers a reduction in SGC cell aggressiveness.
ID2 therefore represents a potential therapeutic target during SGC progression.

Academic Significance and Societal Importance of the Research Achievements

ヒト口腔癌の約85％は扁平上皮癌であり、残りの15％を唾液腺癌、肉腫が占めている。唾液腺癌が口腔癌に占める割合は少ないが、放射線化学療法の感受性が良好な扁平上皮癌と対し、唾液腺癌は外科的切除以外、現在有効な治療法が確立されていない。加えて組織型、細胞特性なども多彩で、それにより浸潤、転移の早さも異なるため、さらに治療を困難にしている。
今回、我々はこの点に着目し、ID2をターゲットとした新規治療により、一般に発育の遅いとされる唾液腺癌の発育をさらに遅らせることで担癌状態での患者QOL向上につながると考えた。