Elucidation of Tumor Immune Evasion Mechanisms in Prostate Cancer by Hyaluronan-degrading enzyme

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09535
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Gifu University (2023); Hirosaki University (2020-2022)
• Principal Investigator: Tobisawa Yuki 岐阜大学, 医学部附属病院, 講師 (70623768)
• Co-Investigator(Kenkyū-buntansha): 中根 慶太 岐阜大学, 大学院医学系研究科, 准教授 (00566482)
• Project Period (FY): 2021-01-01 – 2024-03-31
• Keywords: ヒアルロン酸 / ヒアルロン酸分解酵素 / 腫瘍免疫

Outline of Final Research Achievements

Cancer continues to affect an increasing number of people, and while research on cancer proliferation mechanisms and malignancy processes has progressed, many aspects remain unresolved. This study focuses on the metabolism of hyaluronic acid, a functional glycosaminoglycan abundantly present in the extracellular matrix, to examine its correlation with cancer malignancy mechanisms. We identified that the newly discovered transmembrane hyaluronidase TMEM2 independently degrades hyaluronic acid. Moreover, it was suggested that inhibition of this enzyme’s activity could lead to the malignancy of urological cancers. These findings indicate that the metabolism of hyaluronic acid in the tumor microenvironment may be crucial for cancer survival and malignancy.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では新規ヒアルロン酸分解酵素TMEM2がその分子単独で酵素活性を示すことを明らかにしており、今後この分子の発現異常、活性異常による疾患の発見につながる可能性がある。また癌微小環境でのヒアルロン酸代謝が癌の生存、悪性化に寄与する可能性を示す結果から、このメカニズムを標的とした新規薬剤の開発につながる可能性がある。また、このメカニズムを解明することで、既存薬剤の効果の有無を制御する機構の発見にもつながる可能性があり、学術的意義は高いと考える。