Elucidation of molecular mechanisms of oral cancer stem cell formation formation using 3D-culture device

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K17147
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Kyushu Dental College
• Principal Investigator: Nishimuta Fumika 九州歯科大学, 歯学部, 助教 (20808406)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 口腔がん / スフェロイド / 3次元培養 / がん幹細胞

Outline of Final Research Achievements

To maintain the morphological and genetic characteristics of cancer cells that form microenvironments in tissues, we developed a micro-well chip that can produce uniform and large numbers of spheroids, which is difficult to achieve with conventional low-adherent plates. Oral cancer cells seeded on this device quickly aggregated and formed smooth-edged spheroids, which maintained their morphology even at 5 days of culture. The formed spheroids were mainly composed of viable cells. Compared to the conventional 2-dimensional culture cells, the constituent cells of the spheroids were more stem cell-like and less sensitive to anticancer drugs. Furthermore, the cells outgrowth from the spheroids also maintained their stemness.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

がん幹細胞は、難治性の根源であると考えられ、これらを標的とした治療が新たな治療戦略として注目を集めている。口腔がんに対しても、同様の治療戦略の確立が急務であるが、従来の二次元培養した口腔がん細胞に含まれる幹細胞は20%以下であり、その単離は煩雑である。本申請で開発したマイクロウェルチップは、簡便に口腔がん細胞の幹細胞化が誘導可能であり、幹細胞化の分子機構の解明や、関連分子の標的化による薬剤抵抗性の獲得防止を目剤した治療戦略の提案へと繋がることが期待される。
また同チップはデザインの自由度が高く、がん細胞以外の細胞にも応用可能な汎用性の高い、革新的な三次元培養法を提案できるものと確信している。