| Project/Area Number |
18390530
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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 |
Surgical dentistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
TOTSUKA Yasunori Hokkaido University, Graduate School of Dental Medicine, Professor (00109456)
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| Co-Investigator(Kenkyū-buntansha) |
SHINDOH Masanobu Hokkzido University, Graduate School of Dental Medicine, Professor (20162802)
HIDA Kyoko Hokkaido University, Graduate School of Dental Medicine, Assistant Professor (40399952)
HIGASHINO Fumihiro Hokkaido University, Graduate School of Dental Medicine, Assistant Professor (50301891)
KOBAYASHI Masanobu Hokkaido University, Institute for Genetic Medicine, Assistant Professor (80241321)
OHIRO Yoichi Hokkaido University, Graduate School of Dental Medicine, Assistant Professor (40301915)
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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 |
¥16,740,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2007: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2006: ¥11,800,000 (Direct Cost: ¥11,800,000)
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| Keywords | tumor endothelial cell / human oral carcinoma / human ranal carcinoma / human lung carcinoma / DNA microarray / ヒト口腔癌 |
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| Research Abstract |
Tumor is a genetic disorder, and gene targeting therapy for cancer cells has been conducted. However, tumor gene abnormalities arre complicated, and it is quite difficult to improve efficiency of cancer treatment targeting single gene product.
On the other hand, since neovasculization in tumor stroma is essential for tumor survival and Growth, therapy for disturbing neovasculaizaion would be effective in cancer therapy.
It has been considered that the blood vessels in tumor stroma was composed of normal endothelial cells; however, Hida et al. have reported that tumor endothelial cells have genetically varied character compared to the normal endothelial cells by isolation of tumor endothelial cells from mouth xenograft models of human cancers.
We established human tumor endothelial cells by using magnetic beads method from the operation materials of oral carcinoma, renal carcinoma and lung carcinoma. These cells express CD34 and CD131, and confirmed as endothelial cells. RNA was extracted and DNA microarray has been carried out, and we have identified 70 genes that were upregulated in tumor endothelial cells. We confirmed the expression of these gene product by real-time RT-PCR, Western blotting and immunohistochemisty. Proliferation of tumor endothelial cells was decreased by introducing siRNA into the cells. In addition, we found that motility and proliferative activity of tumor endothelial cells were selectively decreased by Cox-2 inhibitor treatment.
These results imply the significance of targeting tumor endothelial cells for favorable cancer therapy.
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