2011 Fiscal Year Final Research Report
Mesenchymal stem cell therapy targeting glioblastoma stem cell.
| Project/Area Number |
22791343
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Osaka University |
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Principal Investigator |
KIJIMA Noriyuki 大阪大学, 大学院・医学系研究科, 招へい研究員 (80534627)
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| Project Period (FY) |
2010 – 2011
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| Keywords | 悪性神経膠腫 / 癌幹細胞 / 間葉性幹細胞 / 細胞療法 |
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| Research Abstract |
Prognosis of glioblastoma multiforme(GBM) patients still remains poor. To improve it, it is important to identify GBM progenitor cells and target them. In this study, we found that CD166/ ALCAM(Activated Leukocyte Cell Adhesion Molecule) was highly expressed on the CD133^+ GBM progenitor cell populations. In the CD133^+ GBM cell population, CD166/ ALCAM^+ cells were highly enriched with tumor-sphere-initiating cells in vitro. We also found that the frequencies of CD166/ ALCAM-positive cells on tumor specimens were significantly correlated with the WHO histological grade of glioma and the prognosis of GBM patients. The function of CD166/ ALCAM in GBM was also examined. Transfection of CD166/ ALCAM siRNA to U87MG cells significantly increased cell invasion in matrigel invasion assay without affecting cell proliferation. Furthermore, over-expression of soluble CD166/ ALCAM in U87MG GBM cells promoted tumor progression in intracranial transplant to immune-deficient mice. In summary, CD166/ ALCAM can be a new GBM progenitor marker and also a prognostic marker, and is involved in the regulation of GBM invasion. In addition, soluble CD166/ ALCAM which is also expressed in GBM cells, promote GBM invasion, suggesting that soluble CD166/ ALCAM is a potent therapeutic target against GBM. Now we are investigating whether soluble CD166/ ALCAM is a potent therapeutic target for mesenchymal stem cell therapy.
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