Detection of key modulators of lung cancer associated fibroblast for targeted therapies
| Project/Area Number |
19K17683
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Juntendo University |
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Principal Investigator |
Namba Yukiko 順天堂大学, 医学部, 講師 (90782243)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 腫瘍関連線維芽細胞 / ITGA11 / COL11A1 / 非小細胞肺癌 / TGFβ1 / 癌関連線維芽細胞 / TGFβ１ / 肺癌 |
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| Outline of Research at the Start |
肺癌における癌進展抑制のため、組織中のCAFの生物学的特性を分析し、CAFを標的とした新規治療法の開発への基盤形成までを目的とする。CAFの標的因子を同定し、CAFと肺癌細胞の共移植マウスモデルを用いてCAF標的治療の奏功性を評価する。本研究により
① CAFを介する癌進展の特性を解明できる。
② CAFの特性に基づいた感受性の高い治療標的を同定。
③ CAFを標的とする治療効果の予測が可能となる。
といった成果が得られる。
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| 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.
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| 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。
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Report
(5 results)
Research Products
(4 results)
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[Journal Article] Multiple Types of Taste Disorders among Patients with COVID-192022
Author(s)
Nanjo Yuta、Okuma Tomoko、Kuroda Yumi、Hayakawa Eri、Shibayama Kohei、Akimoto Takashi、Murashima Ryoko、Kanamori Koichiro、Tsutsumi Takeo、Suzuki Yohei、Namba Yukiko、Makino Fumihiko、Nagashima Osamu、Sasaki Shinichi、Takahashi Kazuhisa
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Journal Title
Internal Medicine
Volume: 61
Issue: 14
Pages: 2127-2134
DOI
ISSN
0918-2918, 1349-7235
Year and Date
2022-07-15
Related Report
Peer Reviewed / Open Access
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