Fibroblast-dependent cancer cell invasion

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19488
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: National Cancer Center Japan
• Principal Investigator: Genichiro Ishii 国立研究開発法人国立がん研究センター, 先端医療開発センター, 分野長 (00270869)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 線維芽細胞 / がん幹細胞 / 浸潤

Outline of Final Research Achievements

To clear whether podoplanin-positive cancer stem cells in squamous cell carcinoma have higher invasion activity during a fibroblasts-dependent invasion, we performed a collagen gel invasion assay using fluorescent ubiquitination-based cell cycle indicator-labeled A431 cells. The total number and number of invading cells in S/G2/M phase were counted using time-lapse imaging cocultured with fibroblasts. There was no significant difference between the number of invading podoplanin-positive and negative A431 cells when fibroblasts did not exist. On the contrary, the number of invading podoplanin-positive cells was significantly higher when fibroblasts existed. Knockdown of podoplanin decreased the number of invaded A431 cells significantly when fibroblasts existed. Podoplanin-positive A431 cells display higher invasion activity when fibroblasts exist, suggesting that some biological functions of cancer stem cells might become evident only within the fibrous tumor microenvironment.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

一般にがん幹細胞は高い浸潤・遊走能を持つとされているが、本検討では線維芽細胞依存的な浸潤においてのみ、がん幹細胞の浸潤が促進されていた。このことは、がん幹細胞を標的とする治療法を考える上では、がんの微小環境、すなわち、非がん細胞である間質細胞の存在をも考慮すべきであることを示している。