Nerve/tumor interaction during perineural invasion of human oral carcinoma cells in mouse tongue xenograft model

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11529
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: The Nippon Dental University
• Principal Investigator: SOENO Yuuichi 日本歯科大学, 生命歯学部, 教授 (70350139)
• Co-Investigator(Kenkyū-buntansha): 島津 徳人 麻布大学, 生命・環境科学部, 准教授 (10297947) ; 田谷 雄二 日本歯科大学, 生命歯学部, 准教授 (30197587) ; 白子 要一 日本歯科大学, 生命歯学部, 助教 (50756377) ; 佐藤 かおり 日本歯科大学, 生命歯学部, 講師 (90287772)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 病理学 / 扁平上皮癌 / 癌微小環境 / 神経浸潤 / 同所移植モデル

Outline of Final Research Achievements

To investigate the cellular and molecular bases of nerve/tumor interactions during tumor progression, we transplanted oral carcinoma cell line HO-1-u-1 into the tongue of nude mice and determined tumor growth and micro-metastatic dissemination. HO-1-u-1 was tumorigenic in mouse tongue and showed low (< 40%) metastatic potential. HO-1-u-1 tumors displayed a unique invasion mode: tumor cells grew in a cord-like fashion, penetrated into the intermuscular spaces, and in particular, exhibited active perineural invasion. The prominent vimentin expression in HO-1-u-1 tumors at the periphery of the tumor mass and was maintained in nodal metastatic sites. Three-dimensional reconstruction highlighted the perineural invasive property in tumor microenvironment. Based on 2D and 3D histological observations, we found that HO-1-u-1 provided a useful model of oral cancer development with respect to perineural invasion.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

これまで神経と口腔癌細胞との相互作用を解析するモデルは希少であり、多くは唾液腺組織に由来する腺様嚢胞癌での神経浸潤例を用いるにとどまっていた。HO-1-u-1移植ではマウス舌組織において再現性高く神経浸潤を起こすことから、神経－癌細胞間相互作用を解析するうえで画期的なIn vivo実験系となる。今後の癌浸潤、癌性疼痛の研究推進に寄与できると考えている。