Detection of key modulators of lung cancer associated fibroblast for targeted therapies

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17683
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Juntendo University
• Principal Investigator: Namba Yukiko 順天堂大学, 医学部, 講師 (90782243)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 腫瘍関連線維芽細胞 / ITGA11 / COL11A1 / 非小細胞肺癌 / TGFβ1

Outline of Final Research Achievements

We elucidated the functional regulation and cancer progression mechanism mediated by ECM which is produced by CAF by comparing them to normal lung fibroblasts isolated from same patients. When comparing the migration ability of normal lung fibroblasts and CAFs isolated from the same patient, the migration ability mediated by CAF-produced fibronectin and Type I Collagen was high in CAFs. CAGE analysis revealed the expression of ITGA11 and COL11A1 were high in CAFs. Also as s a result of Western blotting, we found that both expression were high in CAFs at the protein level. Furthermore, conditioned media from A549 cultures significantly stimulated ITGA11 expression and harvested media from CAFs significantly stimulated migration of A549 compared to that of normal fibroblasts. This suggests that ITGA11 in the cancer stroma is a factor that contributes to the progression of cancer by regulating migration ability, and might be a new therapeutic target focused on the cancer stroma.

Free Research Field

呼吸器全般

Academic Significance and Societal Importance of the Research Achievements

本研究ではインテグリンα11 +/コラーゲンタイプXIαI + CAFの活性化が肺がんの進展に特に重要な役割を担っている可能性を明らかにした。本研究成果は、CAF を標的とした分子標的治療法の基盤形成をなす研究である。将来的に肺癌患者の実地治療に多大なる効果が期待され癌患者の生命予後の改善につながり学術的意義は非常に大きい。今後さらに研究を重ねることで、CAFの機能解明に関する研究は 肺がん死亡者数の減少を導くブレークスルーとなりうることが期待される。