Isolation and culture of human terminal respiratory unit epithelial stem cells and elucidation of underlying tumorigenesis mechanisms of lung adenocarcinoma

2016 Fiscal Year Final Research Report

• Project/Area Number: 26861134
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory surgery
• Research Institution: National Cancer Center Japan
• Principal Investigator: Yamada Kenji 国立研究開発法人国立がん研究センター, 研究所, 外来研究員 (70645069)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肺癌 / TRU-type 肺腺癌 / TTF-1 / p63 / 組織幹細胞 / 培養法 / Wntシグナル / 発がんモデル

Outline of Final Research Achievements

Recent studies revealed that lung adenocarcinoma originates in terminal respiratory unit (TRU-type ADC) is prevalent among non-smokers and frequently harbors driver oncogenic gene mutations represented by EGFR mutation. Anti-smoking campaigns are less effective in preventing this type of adenocarcinoma, therefore the development of new strategies for prevention or eradication is needed. In this study, I modified a recently introduced cell culture method and succeeded to establish two types of TTF-1 positive normal human TRU epithelial cells. One is TTF-1/p63 double-positive (DP) and the other is TTF-1 single-positive (TTF-1 SP). I partially characterized the former cells that have been underrecognized to date. I propose that the DP cells are TRU-type epithelial stem cells and the cells-of-origin of TRU-type ADC. This concept could explain some characteristics of TRU-type ADC from the point of view of cellular mechanisms.

Free Research Field

診断病理学、実験病理学、呼吸器病学、分子細胞生物学