2006 Fiscal Year Final Research Report Summary
Identification of Cancer Stem Cells and Its Clinical Application for Treating Aggressive Neuroblastomas
| Project/Area Number |
17390473
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | Chiba Cancer Center Research Institute |
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Principal Investigator |
NAKAGAWARA Akira Chiba Cancer Center Res. Inst., Director, 研究局, 研究部長 (50117181)
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| Co-Investigator(Kenkyū-buntansha) |
TAKENOBU Hisanori Chiba Cancer Center Res. Inst., Division of Pathology, Researcher, 病理研究部, 研究員 (60392247)
OZAKI Toshinori Chiba Cancer Center Res. Inst., Division of Biochemistry, Senior Researcher, 生化学研究部, 上席研究員 (40260252)
OHIRA Miki Chiba Cancer Center Res. Inst., Division of Biochemistry, Research scientist, 生化学研究部, 研究員 (20311384)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Neuroblastoma / Cancer stem cells / Stem cell markers / nestin / CD 133 / XCE / p73 / p63 |
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| Research Abstract |
1. Identification of neuroblastoma stem-like cells marker genes
Three cell lines with characteristic phenotype, N-, I-and S-type cells, were subcloned from the neuroblastoma cell lines at Sloan-kettering Cancer Hospital. By using our in-house cDNA microarray carrying 5300 cDNAs, we have identified more than several genes specifically expressed in I-type cells which are believed to be very close to the neuroblastoma stem cell.
2. Expression of cancer stem cells markers in neuroblastomas in primary culture
To search for the neuroblastoma stem cells, we used 34 neuroblastomas in primary culture as well as 6 neuroblastoma cell lines. Most of the primary neuroblastoma cells formed spheres, in which some cells were positive for sustained BrdU labeling, suggesting the presence of cancer stem cells of neuroblastoma. We then tested the significance of the potential markers of neuroblastoma stem cells in primary culture cells. Both nestin and TUJ1 were preferentially positive in favorable tumor cells as compared to unfavorable cells. Especially, expression of nestin was significantly high in tumor cells obtained from patients under one year of age. Expression of p75NTR also showed the similar pattern, but its expression levels were relatively low. Interestingly, both p63 and p73, the variants of p53 tumor suppressor, were highly expressed in many. neuroblastoma cells in primary culture independently of the tumor stages. Therefore, they could be new stem cell markers which might initiate the genesis of neuroblastoma. The further study about the functional roles of their variants, the TA form and the delta-N form, should be needed.
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[Journal Article] Decreased expression of pro-apoptotic BMCCl, a novel gene with the BNIP2 and Cdc42GAP homology (BCH) domain, is associated with poor prognosis in human neuroblastomas.2006
Author(s)
Machida T, Fujita T, Ooo M L, Ohira M, Isogai E, Mihara M, Hirato J, Tomotsune D, Hirata T, Fujimori M, Adachi W, Nakagawara A.
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Journal Title
Oncogene
Pages: 25:1931-1942
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression profiling using a tumor-specific cDNA microarray predicts the prognosis of intermediate-risk neuroblastomas.2005
Author(s)
Ohira M, Oba S, Nakamura Y, Isogai E, Kaneko S, Nakagawa A, Hirata T, Kubo H, Goto T, Yamada S, Yoshida Y, Fuchioka M, Ishii S, Nakagawara A.
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Journal Title
Cancer Cell
Pages: 7:337-350
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] LMO3 interacts with neuronal transcription factor, HEN2, and acts as an oncogene in neuroblastoma.2005
Author(s)
Aoyama M, Ozaki T, Inuzuka H, Tomotsune D, Hirato J, Okamoto Y, Tokita H, Ohira M, Nakagawara A.
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Journal Title
Cancer Res.
Pages: 65:4587-4597
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Neuroblastoma2005
Author(s)
Nakagawara A.
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Journal Title
Chapter 5. Molecular and developmental biology of neuroblastoma.
Pages: 41-53
Description
「研究成果報告書概要(欧文)」より
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