Carcinogenic mechanisms of stem cells in inflammation-related cancer and its prevention

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05255
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene and public health
• Research Institution: Mie University
• Principal Investigator: Murata Mariko 三重大学, 医学系研究科, 教授 (10171141)
• Co-Investigator(Kenkyū-buntansha): 及川 伸二 三重大学, 医学系研究科, 准教授 (10277006) ; 翠川 薫 三重大学, 医学系研究科, リサーチアソシエイト (20393366) ; 平工 雄介 福井大学, 学術研究院医学系部門, 教授 (30324510)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: がん / 炎症 / 幹細胞 / 8-ニトログアニン / エピゲノム異常

Outline of Final Research Achievements

Under chronic inflammation, reactive oxygen / nitrogen species are produced from both inflammatory cells and epithelial cells. Inflammation-related cancers are characterized by mutagenic DNA lesions, such as 8-nitroguanine, accumulation of mutation, and epigenetic alteration. Tissue injury may activate stem cells for tissue regeneration under inflammatory microenvironment.
We demonstrated that indium compounds induced inflammation-specific 8-nitroguanine formation in lung epithelial cells via HMGB1-RAGE pathway. We found the formation of 8-nitroguanine in stem cell marker CD44v6 and ALDH1A1-positive cancer cells. Liker fluke-infested cholangiocarcinoma (CCA) exhibited a higher level of CD44v9 expression than in sporadic CCA tissues, and no CD44v9 staining in the normal bile duct cells. We observed significantly higher expression of inflammation-related markers, S100P and COX-2, in liker fluke-infested CCA tissues. It is suggested that inflammation may associate cancer stem cells.

Free Research Field

環境腫瘍学

Academic Significance and Societal Importance of the Research Achievements

感染症および慢性炎症が全世界の発がん要因の約25%を占めると推定されている。本研究の成果として、炎症が幹細胞がん化に寄与する可能性が示されたことは、抗炎症物質ががん予防に有効である疫学研究結果を支持するものであり、学術的意義は高い。また、炎症を促進する経路のリガンドとしてHMGB1やS100Pの寄与を明らかにしており、これらを標的とする創薬がなされれば、社会的意義は大きい。