Pathological analysis of HYBID-mediated hyaluronic acid metabolism involved in the tumor microenvironment creation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07422
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Jikei University School of Medicine (2021); Keio University (2019-2020)
• Principal Investigator: Shimoda Masayuki 東京慈恵会医科大学, 医学部, 教授 (70383734)
• Co-Investigator(Kenkyū-buntansha): 西村 知泰 慶應義塾大学, 保健管理センター(日吉), 講師 (90348649)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: がん微小環境 / ヒアルロン酸代謝 / 線維芽細胞 / 免疫細胞

Outline of Final Research Achievements

Hyaluronan (HA) plays an important role in the development and maintenance of tissues, and its degradation is implicated in many pathologic conditions. We recently reported that HA-binding protein involved in HA depolymerization (HYBID) is a key molecule in HA depolymerization, but its developmental and pathologic functions remain elusive. In this project, we analyzed the relationship between HYBID-mediated hyaluronic acid metabolism and the tumor microenvironment. Using the tumor xenograft model, the different tumorigenicity were observed between Hybid-deficient and wild-type mice. Histologically, increased hyaluronic acid deposition was observed around the tumor, and polymerized hyaluronic acid was increased in the culture supernatant of Hybid-deficient stromal cells. These results suggest that stromal cell-derived HYBID is involved in the tumorigenesis via hyaluronan acid degradation.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

高分子ヒアルロン酸は実用化に成功した細胞外マトリックスの一つであるが、その生体内での詳細な代謝機構は未だ解明されていない。生理的・病的状態において多岐にわたる作用を発揮することが推測されるHYBIDによるヒアルロン酸分解系機構の解明は、様々な疾患の治療や予防に役立つ可能性があると考えられる。本研究成果は、ヒアルロン酸分解制御に基づくがんに対する治療法開発の基礎的データとなりうる可能性があると考えている。