2021 Fiscal Year Final Research Report

Cell competition at the lateral invasion front of oral squamous cell carcinoma

Research Project

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Project/Area Number	19K10101
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57020:Oral pathobiological science-related
Research Institution	Fukuoka Dental College
Principal Investigator	Saku Takashi 福岡歯科大学, 口腔歯学部, 客員教授 (40145264)
Co-Investigator(Kenkyū-buntansha)	北河憲雄福岡歯科大学, 口腔歯学部, 講師 (40628517) 阿部達也新潟大学, 医歯学系, 助教 (70634856) 吉本尚平福岡歯科大学, 口腔歯学部, 講師 (70780188)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	口腔がん / 細胞死 / 細胞競合 / 扁平上皮癌 / 扁平苔癬 / 異角化 / 循環不全 / 酸化ストレス
Outline of Final Research Achievements	Based on our histopathological recognition of cell death occurring at the invasion front of oral squamous cell carcinoma cells against non-cancerous epithelial cells, we formulated a hypothesis that those dead cells are resulted from cell competition between them. We investigated the significance and cell machinery of cell death at the invasion interface using morphofunctional analyses, and showed that oral squamous cell carcinoma cells were activated by their own autophagacytosis of neighboring apoptotic carcinoma cells via a Rac1-dependent manner and that LAD1 functioned in filopodia/lamellipodia formation of carcinoma cells to form actin arc with actin filaments towards the lateral direction of invasion. In addition, we found that hyaline bodies arising at the invasion interface resembled Civatte bodies of oral lichen planus in terms of shape and possible generation route through dyskeratosis. Dyskeratotic features were shown to be useful in cytological diagnosis of oral malignancy.
Free Research Field	口腔病理学
Academic Significance and Societal Importance of the Research Achievements	細胞競合で生じる細胞死の分子機序の一つとして、扁平上皮癌死細胞を同種癌細胞がRac1依存的に貪食して癌細胞が活性化することを明らかにしたが、この死細胞貪食機序が制癌対策に応用できる可能性を見出した。浸潤界面で癌細胞に高発現するLAD1がアクチン線維と共同して仮足形成に関与するすることが判明したので、LAD1の機能を消失させることによって、癌細胞の浸潤を抑制するという抗癌対応の可能性を示しえた。さらに、浸潤界面における硝子体出現が異角化現象による新たな細胞死経路であることを明らかにし、細胞死研究に新たな方向性を示し、細胞診の臨床現場で異角化所見を悪性判定指標とすることの有用性を提唱できた。