Elucidation of the mechanism of lung cancer stem cell transformation and treatment resistance

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16527
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Kanazawa Medical University
• Principal Investigator: MOTONO Nozomu 金沢医科大学, 医学部, 講師 (30634901)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 肺癌 / 幹細胞 / スフィンゴリン脂質 / TSHZ2

Outline of Final Research Achievements

To verify the differential expression of Teashirt homolog 2(TSHZ2) in different adenocarcinoma cell lines, PC9 and A549 cell lines were treated and TSHZ2 expression was assessed by Western blotting. TSHZ2 expression was upregulated in PC9 cell lines treated with pDsRed-monomer-C1-TSHZ2, whereas TSHZ2 expression was attenuated in A549 cell lines treated with siRNA-TSHZ2. Overexpression of TSHZ2 in PC9 cell lines significantly suppressed cell proliferation compared with cells treated with pDsred-monomer-C1-empty. Furthermore, cells treated with pDsred-monomer-C1-TSHZ2 formed only about 100 clones over the next 14 days, which was significantly less than the others. In addition, when the effect of TSHZ2 expression on apoptosis was evaluated by flow cytometry, the number of apoptotic cells was significantly higher in the PC9 cell line treated with pDsred-monomer-C1-TSHZ2 compared to the control group.

Free Research Field

呼吸器外科

Academic Significance and Societal Importance of the Research Achievements

予後不良を引き起こす因子が癌幹細胞の活性化に関与するとの仮説を立てて、肺癌の多くを占める肺腺癌を標的とし、癌の浸潤・増殖および予後に影響を及ぼす因子を解析した。TSHZ2の発現低下による増殖能の活性化、アポトーシスの抑制を確認した。以前の研究でSPHK1が肺癌の浸潤部のfibroblastで高発現することで増殖能が活性化すること、SPHK1高発現例は予後不良となる傾向も認めている。今後、これらの因子が肺癌の癌幹細胞の活性化に寄与するかを検証・解明し創薬につなげることができれば、治療抵抗性の肺癌の治療成績を劇的に向上させる可能性がある。