A search for the characteristic molecules of oral squamous cell carcinoma stem cells by generating organoid-like structures

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18489
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: The Nippon Dental University
• Principal Investigator: Hirashima Kanji 日本歯科大学, 生命歯学部, 助教 (50824661)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がん幹細胞 / リプログラミング / iPS細胞 / 口腔扁平上皮癌

Outline of Final Research Achievements

The purpose of this study is to develop a new treatment method targeting oral squamous cell carcinoma (OSCC) stem cells by using organoid culture technology. First, we transduced four reprograming factors, Oct3/4, Sox2, Klf4, L-myc, into the OSCC cell lines HSC-3-M3(metastatic lingual carcinoma), HSC-3(lingual carcinoma), KON(oral floor carcinoma), Ca9-22(gingival carcinoma). Tra-1-60 positive cells were obtained from reprogrammed OSCC cells showed cancer stem cell (CSC) properties, including ES/iPS cell like colony formation and increasing expressions of CSC markers. Organoid-like structures and 5-FU resistant cells were successfully prepared from Tra-1-60 positive reprogrammed OSCC cells.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

本研究は、口腔扁平上皮癌(OSCC)幹細胞による腫瘍組織構築のプロセスを明らかにし、口腔癌幹細胞に対する新規治療法の開発につなげようとする点に特色と意義を持つ。これまで困難を極めてきた癌幹細胞の特性分子の探索に向け、OSCC細胞のリプログラミングによる分化段階の巻き戻しと、Tra-1-60陽性細胞のソーティングによる幹細胞様の性質を具有する細胞の維持培養法の確立、三次元培養によるOSCCオルガノイド様細胞集塊の誘導を行った。この結果を踏まえ、OSCC幹細胞の特性分子を明らかにし、腫瘍組織構築プロセスやOSCC幹細胞の治療標的分子の解明による革新的な分子標的治療法の開発に向けた展開が期待できる。