2011 Fiscal Year Final Research Report
The investigation of individual anti-angiogenic therapy focused on the control mechanism of matrix remodeling in renal cell carcinoma
| Project/Area Number |
21590590
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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 |
Applied pharmacology
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| Research Institution | Kyoto University |
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Principal Investigator |
KAMBA Tomomi 京都大学, 医学研究科, 講師 (20402836)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Osamu 京都大学, 医学研究科, 教授 (90260611)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 腎細胞癌 / マトリックス・リモデリング / 抗血管新生療法 / VHL / JunB / MMP-2/9 / CCL2 |
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| Research Abstract |
The purpose of this research is to identify a pathway of the control mechanism of matrix remodeling in renal cell carcinoma and to examine whether it could be a new therapeutic target and a sensitive marker of anti-angiogenic therapy. This study indicates that the pathway of VHL-atypical PKC-JunB not through the HIF(hypoxia-inducible factor) contributes to the progression of renal cell carcinoma, and we actually confirmed with xenografts from kidney cancer cell lines that the expression of JunB affected tumor growth and angiogenesis. Moreover, we identified matrix metalloproteinase-2(MMP-2), MMP-9 and chemokine(C-C motif) ligand-2(CCL2) as downstream effectors of JunB. The results of their functional analysis suggest that they have the possibility to be new molecular targets for angiogenesis and invasion of renal cell carcinoma.
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