Treatment with new biological concept for virus-associated head and neck cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19557
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Yoshizaki Tomokazu 金沢大学, 医学系, 教授 (70262582)
• Co-Investigator(Kenkyū-buntansha): 近藤 悟 金沢大学, 附属病院, 講師 (70436822)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: ウイルス発癌 / Epstein-Barr ウイルス / ヒトパピローマウイルス / 細胞競合

Outline of Final Research Achievements

In the cell competition between the nasopharyngeal carcinoma (NPC) cells and the surrounding epithelial cells, the former was identified as the WINNER, and the latter as the LOSER which express anti-apoptotic factor SPARC. Culture condition can modify this cell competition. We revealed that addition of resveratrol replaced the WINNER with the LOSER, as a result, HK1-EBV cells were eliminated by HK1 cells. EBV-encoded LMP1 strongly influenced the competition property. The LMP1 positive cells excreted exosomes that contain SPARC-inducing molecules. These exosomes were incorporated in the surrounding normal cells, resulting in SPARC expression in the cells.

Free Research Field

耳鼻咽喉科・頭頸部外科

Academic Significance and Societal Importance of the Research Achievements

生物発生学における細胞競合理論を癌生物学に応用が試みられてまだ日が浅い今日、EBV陽性上咽頭癌組織においても癌細胞と周辺細胞との間に細胞競合が生じていることを初めて解明した点で意義がある。さらに、がんという立場よりもEBV感染細胞と非感染細胞という視点からの細胞競合と捉え、細胞競合誘導機構としてEBV感染細胞から分泌されるエクソソームに内包される物質がその担い手であることを解明した点は独創性が高い。そして、抗酸化作用を有するレスベラトロール添加が勝者と敗者を逆転させることから、前癌病変の段階での発癌抑制に応用可能であることを明らかにした点で社会還元性が高い。