2011 Fiscal Year Final Research Report
Exploitation of gene-targeting therapy based on the cellular and biological features of oral-carcinoma stem cell and tumor microenvironment.
| Project/Area Number |
20249079
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SHINDOH Masanobu 北海道大学, 大学院・歯学研究科, 教授 (20162802)
HIGASHINO Fumihiro 北海道大学, 大学院・歯学研究科, 准教授 (50301891)
HIDA Kyoko 北海道大学, 大学院・歯学研究科, 特任准教授 (40399952)
KITAMURA Tetsuya 北海道大学, 大学院・歯学研究科, 助教 (00451451)
OHBA Yusuke 北海道大学, 大学院・医学研究科, 准教授 (30333503)
MATSUMOTO Kenichi 島根大学, 総合科学研究支援センター, 教授 (30202328)
OHIRO Yoichi 北海道大学, 大学院・歯学研究科, 助教 (40301915)
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| Project Period (FY) |
2008 – 2011
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| Keywords | 口腔癌 / 癌の微小環境 / 癌幹細胞 / 上皮間葉移行 |
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| Research Abstract |
We have shown that the tumor endothelial cells which exist in cancer stroma have a different gene background from normal endothelial cells. It has been becoming clear that epithelial-mesenchymal transition (EMT) plays an important role in tumor invasion and metastasis. It is expected that the investigation on the interaction of the oral squamous cell carcinoma cell in epithelium nature and a mesenchymal cell will contribute to the establishment of effective therapeutic method because stromal cells have the ability to supply nutrition and oxygen to a tumor. HuR protein usually exists in the nucleus, and HuR is participating to stabilize AU-rich element (ARE) mRNA. We showed that ARE mRNA is stabilized through HuR by a viral carcinogenesis system that concerns cell transformation. Oral environment has a unique features including distinct organs such as salivary glands. We identified that RANKL, an osteoclast inducer, expression was higher in oral environment. Furthermore, when oral cancer cells were implanted in oral region of nude mice, cancer cells proliferated intentionally, and EMT was observed. Tumor microenvironment is deeply correlated with cancer cell proliferation and invasion/metastasis. We have isolated endothelial cells in tumor stroma, and investigated the biological feature of tumor endothelial cells. As a result, tumor angiogenesis was suppressed by inhibiting Cox-2 known also for the factor inducing inflammation, and the resistance for chemothrapy was acquired by MDR1 upregulatin caused by VEGF signaling
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[Journal Article] Biglycan is a specific marker and an autocrine angiogenic factor of tumor endothelial cells2012
Author(s)
Yamamoto K, Ohga N, Hida Y, Maishi N, Kawamoto T, Kitayama K, Akiyama K, Osawa T, Kondoh M, Matsuda K, OnoderaY, Fujie M, Kaga K, Hirano S, Shinohara N, Shindoh M, Hida K
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Journal Title
Br J Cancer
Volume: 106
Pages: 1214-1223
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[Journal Article] HuR keeps an angiogenic switch on by stabilizing mRNA of VEGF and COX-2 in tumor endothelium2011
Author(s)
Kurosu T, Ohga N, Hida Y, Maishi N, Akiyama K, Kakuguchi W, Kuroshima T, Kondo M, Akino T, Totsuka Y, Shindoh M, Higashino F, Hida K
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Journal Title
Br J Cancer
Volume: 104
Pages: 819-829
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[Journal Article] Cytogenetic abnormalities of tumor-associated endothelial cells in human malignant tumors2009
Author(s)
Akino T, Hida K, Hida Y, Tsuchiya K, Freedman D, Muraki C, Ohga N, MatsudaK, Harabayashi T, Shinohara N, NonomuraK, Klagsbrun M, Shindoh M
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Journal Title
Am J Pathol
Volume: 175
Pages: 2657-2667
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