| Project/Area Number |
18591439
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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 |
General surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
KUBO Makoto Kyushu University, University Hospital, Assistant Professor (60403961)
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| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Masasyuki Kyushu University, University Hospital, Assistant Professor (90380394)
AKASHI Kouichi Kyushu University, University Hospital, Professor (80380385)
黒木 祥司 九州大学, 大学病院, 講師 (30215090)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,960,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | cancer stem cell / breast cancer / anticancer-drug resistant / morphogenesis signais / side population / CD44+24- / low cell / estroren receptor |
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| Research Abstract |
It has been hypothesized that a tumor generates from cancer stem cells (CSC) possessing both self-renewal. and differentiation potential. We need to develop and establish therapeutic strategies for CSC to perform effective and persistent treatment, because the carcinoma tissue consists of both differentiated and undifferentiated one; the former is anticancer-drug sensitive and the latter is anticancer-drug resistant as CSC. Therefore, a purpose of this study is that we identify CSC to develop treatment for CSC. (1) The Side population (SP) and the CD44+/CD24-/lowpopulation were enriched using cell sorter from human breast carcinoma cell lines. (2) Both populations were confirmed to be resistant to Paclitaxel. (3) We found strong relation between SP cells and CD44+24-/low cells. The CD44+24-/low cells ratio is usually around 16%, but increases with 46% in the SP remarkably. (4) The morphogenesis signals (Wnt, Notch, Hedgehog [Hh]) were highly expressed in CSC by real-time PCR and Immuno-blotting. (5) We confirmed the crosstalk between the Hh and the estrogen receptor signaling pathway which was representative in the breast cancer (Koga K, et. al. 2008). (6) The growth of SP cells and CD44+24-/low cells was effectively suppressed by the antibody for Patched1, receptor of the Hh signaling pathway, which was developed in our department. Thus, we conclude that the Hh signaling pathway is essential for breast CSC which is anticancer-drug resistant.
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