2013 Fiscal Year Final Research Report
Development of a novel conservative therapeutic modality for patients with bone metastasis focusing on hyaluronan network
| Project/Area Number |
23592181
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
NISHIDA Yoshihiro 名古屋大学, 医学(系)研究科(研究院), 准教授 (50332698)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKUSHI Satoshi 名古屋大学, 医学系研究科, 寄附講座講師 (90378109)
URAKAWA Hiroshi 名古屋大学, 医学系研究科, 特任助教 (60584753)
ARAI Eisuke 名古屋大学, 医学部附属病院, 医員 (40612841)
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| Co-Investigator(Renkei-kenkyūsha) |
SHINOMURA Tamayuki 東京医科歯科大学, 医歯学総合研究科, 准 教授 (70206118)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 糖鎖 / 骨転移 / ヒアルロン酸 / 保存的治療 / 遺伝子改変マウス |
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| Research Abstract |
We established mouse bone metastasis model of breast and lung cancer, and revealed that metastatic lesion in bone had marked expression of hyaluronan in both malignant cells and stromal cells including tumor-associated fibroblasts. 4- Methylumbelliferone (4-MU), an inhibitor of hyaluronan synthesis significantly suppressed the hyaluronan synthesis of breast and lung cancer as well as stromal fibroblast, resulting in the suppression of metastatic lesion in bone. 4-MU also affected the cellular event via suppression of hyaluronan synthesis, that co-localization of CD44, a cell surface receptor of hyaluronan, ezrin, and actin was abrogated by 4-MU.
4-MU had synergistic inhibitory effects on the progression of bone metastasis, with zoledronic acid, a bisphosphonate, which is allowed to use for patients with bone metastasis in Japan. 4-MU also had synergistic effects with radiotherapy, a conventional anti-bone metastatic treatment.
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