Investigation for mechanism of metastasis using molecular imaging

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09571
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kanazawa University
• Principal Investigator: Tuchiya Hiroyuki 金沢大学, 医学系, 教授 (40227434)
• Co-Investigator(Kenkyū-buntansha): 三輪 真嗣 金沢大学, 医学系, 助教 (40753455) ; 林 克洋 金沢大学, 医薬保健学総合研究科, 特任教授 (80507054) ; 五十嵐 健太郎 金沢大学, 医薬保健学総合研究科, 特任助教 (80622860) ; 山本 憲男 金沢大学, 医薬保健学総合研究科, 特任教授 (90332668)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 骨肉腫 / 転移 / エクソソーム

Outline of Final Research Achievements

The roles of small extracellular vesicles (SEVs) in enhancing metastases have been demonstrated in multiple tumors, but they are still poorly understood in osteosarcoma. Hence, this study investigated the effects of SEVs on progression and the tumor microenvironment in mice and patients. In an orthotopic implantation study, we found that osteosarcoma-derived SEVs had the potential to enhance metastases and angiogenesis. In addition, osteosarcoma-derived SEVs decreased the number of mature osteoclasts in vivo. In vitro osteoclastogenesis studies revealed that the inhibition of osteoclast maturation by osteosarcoma-derived SEVs was mediated by suppressing the NF-κB signal pathway. MicroRNA analysis of SEVs from different malignant human osteosarcomas revealed that miR-146a-5p was involved in the inhibition of osteoclastogenesis. In osteosarcoma patients, lower numbers of osteoclasts in biopsy specimens at the first visits were correlated with higher malignancy.

Free Research Field

骨軟部腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究は骨肉腫におけるエクソソーム，miRNA，マクロファージ，破骨細胞の役割を明らかにすることで骨肉腫の進展・転移機序を解明する研究である。miRNAは骨肉腫の診断バイオマーカーとなる可能性があり，また，エクソソームやマクロファージ，破骨細胞は骨肉腫の治療標的となる可能性があり，新たな診断・治療方法の開発へと発展することが期待される。