2014 Fiscal Year Final Research Report
The cell diversity and the cell lineage in Shh-type medulloblastoma.
| Project/Area Number |
24501325
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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 |
Tumor biology
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 脳腫瘍 / 小脳髄芽腫 / miRNA / 癌幹細胞 / shh シグナル / Patched-1 / ニューロン分化 / 神経前駆細胞 |
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| Outline of Final Research Achievements |
Our immunohistochemical analyses and genetic lineage study showed that the medulloblastoma (MB) were composed of the MB cells of varied differentiation status, and that the cancer stem cells took the bipolar cell morphology and often differentiated into neurons with multiple dendrites like normal immature cerebellar granule neurons. We found that in MB, the expression patterns of miRNA-Xs that we have identified as the gatekeeper in MB development, were well correlated with the differentiation state of MB cells. Mis-expression of miRNA-X induced the differentiation of MB stem cell lines (in vitro), and the simultaneous inhibition of miRNA-Xs with Ptc1 cKO in granule cell progenitor cells induced the cancer stem cell-dominant MB (in vivo).
These results indicate that miRNA-Xs must be involved in making the hierarchy of MB cells, promising their application to eradicate the cancer stem cells for MB cure.
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| Free Research Field |
分子神経発生学、脳腫瘍生物学
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