Identification of HRG that is highly inhibitory to S100A8/A9-mediated organ tropic cancer metastasis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03516
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Okayama University
• Principal Investigator: Sakaguchi Masakiyo 岡山大学, 医歯薬学域, 教授 (70379840)
• Co-Investigator(Kenkyū-buntansha): 山本 健一 岡山大学, 医歯薬学域, 助教 (00711798) ; 近藤 英作 新潟大学, 医歯学系, 教授 (30252951) ; 豊岡 伸一 岡山大学, 医歯薬学域, 教授 (30397880) ; 木下 理恵 岡山大学, 医歯薬学域, 助教 (40518297) ; 西堀 正洋 岡山大学, 医歯薬学総合研究科, 特命教授 (50135943) ; 村田 等 岡山大学, 医歯薬学域, 講師 (90579096)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: S100A8/A9 / HRG / 転移 / 阻害作用 / がん

Outline of Final Research Achievements

We aimed to study about the fortuitously discovered a metastasis suppression factor against S100A8/A9, plasma histidine-rich glycoprotein (HRG). HRG effectively prevents the binding of S100A8/A9 to the melanoma cell surface, thereby inhibiting the S100A8/A9-induced migration and invasion of melanoma cells at significant levels. When we knocked down HRG in mice bearing melanoma, the brain metastasis was significantly enhanced in addition to the lung. These results suggest that a plasma protein HRG vigorously protects the brain and the lung from the metastasis-threatening of melanoma. We believe that these our original cutting-edge finding largely contributes to solving the complex mechanisms of multiple organ metastasis of cancer cells and to developing HRG-relevant new medicines to overcome and overpower cancer metastasis in the future.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

S100A8/A9によるがん転移の指向性に関わる炎症機転の機構解明には、S100A8/A9受容体群、そしてそれら連携を制御するタンパク質群（HRGが今回の発見）を包括的に理解して初めてその全体像が明らかになると考えられる。従って、代表者グループの新しい発見を基盤とする本課題は、これまでの自他の研究成果を補完し、共に手を取り合い更なる高みを目指せる新たな研究の創造へと発展を遂げていく。