The development of new treatment for gingival cancer considering bone resorption and cancer immunoediting

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K11406
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Saitama Medical University
• Principal Investigator: Nakahira Mitsuhiko 埼玉医科大学, 医学部, 教授 (10253353)
• Co-Investigator(Kenkyū-buntansha): 臼井 通彦 九州歯科大学, 歯学部, 准教授 (10453630) ; 佐藤 毅 埼玉医科大学, 医学部, 准教授 (60406494) ; 星島 宏 埼玉医科大学, 医学部, 助教 (90536781)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 癌治療 / MICA / netrin-4

Outline of Final Research Achievements

We confirmed that human gingival cancer cell line Ca9-22 cells highly expressed MICA gene and protein. DNA microarray analysis in Ca9-22 cells forced expression of MICA gene revealed that 830 genes were upregulated and 27 genes were downregulated. TRAP-positive cells were also found in immediate vicinity of Ntn4-positive vascular endothelial cells during bone healing. We performed drill-hole injury experiments and TRAP staining followed by immunostaining for PECAM-1 at day 14. We also investigated whether Ntn4 expression was changed in the serum of ovariectomized osteoporotic mice. We found that serum Ntn4 levels were significantly decreased in ovariectomized osteoporotic mice. Ntn4 may have a critical role for bone metabolism with characteristic localization.

Free Research Field

耳鼻咽喉科学

Academic Significance and Societal Importance of the Research Achievements

宿主の免疫細胞の表面にはNKG2Dという受容体があり、腫瘍はその発現を抑制する可溶性のMHC（主要組織適合遺伝子複合体）クラスI鎖関連タンパク質A（MICA）を分泌して免疫応答を回避し、抗腫瘍応答を減少させることが知られている。今回の研究からヒト歯肉上皮癌細胞において産生される免疫系細胞を攻撃する分子を制御すること、骨へ浸潤する歯肉上皮癌をnetrin-4が制御できる可能性があることから、今後の癌制御療法に有用であるかもしれない。