2023 Fiscal Year Final Research Report
Determination of the mesenchymal subcluster responsible for carcinogenesis of lung cancer and origin of CAF based on the results of single-cell analysis
| Project/Area Number |
21K08159
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
坪内 拡伸 宮崎大学, 医学部, 助教 (60573988)
小田 康晴 宮崎大学, 医学部, 助教 (90843235)
重草 貴文 宮崎大学, 医学部, 医員 (90867730)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 発がん / シングルセル解析 / 癌微小環境 / 肺癌 / 2型肺胞上皮 / Pten / RhoA / 肺腺癌自然発癌モデル |
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| Outline of Final Research Achievements |
The aim of the this study is to investigate the origins of the tumor microenvironment and tumorigenesis by using a novel model of spontaneous lung adenocarcinoma developed by principal investigator and single cell analysis. In the present study, we have established two mouse models of spontaneous tumorigenesis of lung adenocarcinoma. Lung mesenchymal cells from the unaffected stages of these mice were isolated and subjected to single-cell analysis. Single-cell analysis revealed that emergence of mesenchymal subcluster characterised by high expression of a group of mitochondrial electron-transfer system molecules and exhibiting an epithelial-mesenchymal transition (EMT)-like profile appeared in common in the two spontaneous lung adenocarcinoma models. The electron transport system is the main source of intracellular ROS, suggesting that this mesenchymal subcluster is essential for the initiation of carcinogenesis.
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| Free Research Field |
呼吸器内科
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| Academic Significance and Societal Importance of the Research Achievements |
肺癌を含む癌の発生は、正常な成体幹細胞と遺伝子変異を生じた成体幹細胞との競合に依存する確率的プロセスにより生じる。すなわち、変異した成体幹細胞が癌化するには「周囲の手助け」が不可欠である。癌化の最重要イベントはこの「周囲の手助け」を作ること、「発癌微小環境の形成」であり、有望な癌治療標的となりえるが、いまだ十分に解明されていない。発癌責任サブクラスターと責任パラクラインシグナルが同定されることで、例えば喫煙者などのハイリスク群を対象とした全く新しいがん先制医療の確立が期待される。他臓器の癌、臓器リモデリングの新規治療開発をも加速度的に前進させる。
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