Functional analysis of cancer stroma in the development and invasion of lung cancer using three-dimensional cell culture

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15638
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: The University of Tokyo
• Principal Investigator: Morita Shigeki 東京大学, 医学部附属病院, 登録研究員 (30707021)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 肺癌 / 間質 / 3次元培養 / 浸潤 / 癌関連線維芽細胞

Outline of Final Research Achievements

In this study, we established an invasion model of lung cancer and fibroblast cell line using three-dimensional culture. Additionally, we prepared formalin-fixed paraffin-embedded specimens of the invasion model and immunohistochemically confirmed that cancer-associated fibroblast (CAF) -related factors such as α-SMA and CD10 were upregulated in fibroblasts. We also examined the changes of microRNA expression in fibroblasts by in situ hybridization.
In the investigation of surgical specimens, high expression of CAF-related factors such as calumenin and miR-21 in CAFs were a poor prognostic factor. In addition, functional analysis using cell lines also suggested that they interact and promote invasion of lung adenocarcinoma.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

近年肺癌の研究では間質の変化が注目されてきているが、本研究では3次元培養（層状培養）の新規手法を確立し、癌周囲の線維芽細胞に見られる因子(α-SMA、calumenin等)やmicroRNAの局在、発現の変化を捉えることで、肺腺癌の発生・浸潤過程における間質の役割について新たな知見を加え，補強することになったと考えられる。また、これらの知見は新たな診断マーカーや治療ターゲットにつながる可能性がある。