A trial of miRNAs derived from bone matrix as an inhibitor for bone metastasis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11443
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Hiroshima University
• Principal Investigator: Minamizaki Tomoko 広島大学, 医歯薬保健学研究科, 助教 (30452593)
• Co-Investigator(Kenkyū-buntansha): 吉子 裕二 広島大学, 医歯薬保健学研究科(歯), 教授 (20263709)
• Research Collaborator: Futamura Manabu ; Kozai Katsuyuki ; Ahmed Faisal ; Sarmin Nushrat ; Zaurasari Mentari
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 骨転移 / miRNA / 骨代謝

Outline of Final Research Achievements

We clarified that matrix vesicles and miRNA-125b (miR-125b) inhibit the proliferation, migration and/or invasion of MCF-7 (human breast cancer), PC-3 (human prostate cancer), and PY8119 (mammary adenocarcinoma) cells in vitro. By using bone metastasis models with intratiblal or caudal artery injection to transgenic (Tg) mice overexpressing miR-125b under the control of the human osteocalcin promoter, we analyzed whether miR-125b inhibits bone resorption and/or cancer growth in bones. In both wild-type (WT) and Tg mice, bone resorption and cancer growth were observed within 7 days and 10 days respectively. Based on in vivo imaging and microCT analyses, cancer growth was much higher and bone resorption was much severer in WT mice than in Tg mice, respectively. Histological analysis indicates that the number of TRAP-positive multinucleated cells was higher in WT mice than Tg mice.

Free Research Field

組織学

Academic Significance and Societal Importance of the Research Achievements

骨転移は乳がん、前立腺がん、肺がんに多くみられ、わが国の患者数は15-30万人と推定される。現在では、長期生存するがん患者も多く、骨転移に伴う疼痛、骨折、麻痺などのQOLの低下が問題となっている。現在、少数の治療薬が存在するものの、副作用の問題など選択肢は少ない。微小胞やmiRNAはそれぞれDDSやがんの診断に臨床応用されつつあるが、本件の成果は、生体に本来備わっている骨特異的微小胞と抗腫瘍性miRNAを用いた全く新しい発想に基づく治療のための基礎研究であり、既存のがん患者の骨転移の治療の問題を改善し、より高い効果が期待できる治療法の開発に貢献する。