| Project/Area Number |
26860895
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | Keio University |
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Principal Investigator |
Tanese Keiji 慶應義塾大学, 医学部(信濃町), 助教 (70464815)
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| Research Collaborator |
SAKAMOTO Michiie
Ekmekcioglu Suhendan
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 悪性黒色腫 / CD74 / インターフェロンγ / MIF / 腫瘍微小周囲環境 / インターフェロンガンマ / AKTシグナル / IL-6 / IL-8 / AKT |
|---|
| Outline of Final Research Achievements |
IFN-γ produced by immune cells has a crucial role in tumor immune surveillance; however, it has also been reported to be pro-tumorigenic. In the current study, we found that IFN-γ enhances the expression of CD74, which interacts with its ligand, macrophage migration inhibitory factor (MIF), and thereby activates the PI3K/AKT pathway in melanoma, promoting tumor survival. IFN-γ increased phosphorylation of AKT Ser473 and upregulated total cell surface expression of CD74 in human melanoma cell lines tested. Blockade of CD74-MIF interaction reduced AKT phosphorylation and expression of pro-tumorigenic molecules, including IL-6, IL-8, and BCL-2. Inhibition of CD74-MIF interaction significantly suppressed tumor growth in the presence of IFN-γ in our xenograft mouse model. In the further analysis of Stage III melanoma lymph node metastasis samples, cases expressing MIF showed worse prognosis. Thus, we conclude that IFN-γ promotes melanoma cell survival by regulating CD74-MIF signaling.
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