Establishment of bone metastasis treatment by regulating hyaluronan network and osteoclast

2017 Fiscal Year Final Research Report

• Project/Area Number: 26462261
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya University
• Principal Investigator: Urakawa Hiroshi 名古屋大学, 医学部附属病院, 病院講師 (60584753)
• Co-Investigator(Kenkyū-buntansha): 西田 佳弘 名古屋大学, 医学系研究科, 准教授 (50332698) ; 筑紫 聡 名古屋大学, 医学系研究科, 寄附講座講師 (90378109) ; 小澤 英史 愛知県がんセンター(研究所), 分子病態学部, 研究員 (60635572) ; 新井 英介 名古屋大学, 医学部附属病院, 病院助教 (40612841) ; 生田 国大 名古屋大学, 医学部附属病院, 医員 (40732657) ; 安藤 雄一 名古屋大学, 医学部附属病院, 教授 (10360083)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 転移性骨腫瘍 / 破骨細胞 / ヒアルロン酸 / 骨修飾薬

Outline of Final Research Achievements

Bone metastases impair the quality of patients with malignancies. We focused on the co-effect of regulation of hyaluronan (HA) and bone modifying agents. We investigated the effects of 4-methylumbelliferone (MU) and/or bone modifying agents on HA expression in breast and lung cancer cell lines in addition to their tumorigenicity in vitro and in vivo. MU or zoledronic acid treatment individually suppressed proliferation, migration and invasion of breast and lung cancer cell lines, and combination treatment of MU and zoledronic acid showed synergistic effects. Combination therapy showed additive inhibitory effects on metastatic bone lesions in vivo, which paralleled the inhibition of HA accumulation by MU, and inhibition of osteoclastogenesis. These data suggest that inhibition of HA synthesis is a promising novel therapeutic candidate for bone metastasis in addition to bone modifying agents.

Free Research Field

骨軟部腫瘍