2010 Fiscal Year Final Research Report
Pre-metastatic Niche and Its Role in Lung Metastasis of Malignant Musculoskeletal Tumors
| Project/Area Number |
20591754
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
HASHIMOTO Nobuyuki Osaka University, 医学系研究科, 助教 (50324752)
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| Co-Investigator(Kenkyū-buntansha) |
MYOUI Akira 大阪大学, 医学部附属病院, 准教授 (10263261)
YOSHIKAWA Hideki 大阪大学, 医学研究科, 教授 (60191558)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 悪性骨軟部腫瘍 / 肺転移 / メカニズム |
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| Research Abstract |
We mainly investigated the precise function of a new ubiquitin ligase LUBAC involved in NFκB activation, which is a key molecular event in the early lung metastasis using LM8 murine osteosarcoma animal model. LUBAC was overexpressed in this highly metastatic subclone compared with the parental cells. The media obtained from lung organ culture also stimulated the expression. In the loss of function study, cell proliferation, motility and MMP-9 production was significantly reduced in vitro. And lung metastasis was also inhibited in vivo. When the tumor cells injected from the tail veins were observed by in vivo imaging system, the LUBAC knock-down cells were rapidly washed-out and unable to form early colonization in lung through the suppressed ICAM-1 function. Taken together, we showed an evidence proving that ubiquitination plays an important role not only in protein degradation but also in signal transduction of a human disease.
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