Molecular analysis of bone invasion mechanism in oral carcinoma.
| Project/Area Number |
20791495
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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 |
Surgical dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MORITA Keiichi Tokyo Medical and Dental University, 歯学部・附属病院, 助教 (10396971)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 癌 / 遺伝子 / マイクロアレイ / 顎骨浸潤 / 口腔外科 |
|---|
| Research Abstract |
We investigated the bone invasion in oral squamous cell carcinoma (OSCC) using microarray analyses. Microarray analyses performed on human OSCC specimens revealed that many of the specimens overexpressed PTHrP mRNA, but a few overexpressed IL-6 mRNA. Immunohistochemical analysis revealed that IL-6 was expressed not only in cancer cells but also in fibroblasts and osteoclasts at the tumor-bone interface. Xenografts of HSC3 cells onto the periosteal region of the parietal bone in athymic mice presented histology and expression profiles of RANKL and IL-6 similar to those observed in bone-invasive human OSCC specimens. These results indicate that OSCC provides a suitable microenvironment for osteoclast formation not only by producing IL-6 and PTHrP but also by stimulating stromal cells to synthesize IL-6. As the up-regulation of FADD expression in OSCC microarray analyses and the amplification of 11q13.3 in oral SCC cell lines on the Comparative Genomic Hybridization (CGH) database have be
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come available, genomic amplifications and expression levels of FADD were investigated. The DNA amplifications of FADD were observed in 44.3% cases and were significantly correlated with the histopathological differentiation grade of SCCs. FADD expression levels compared with the matched adjacent epithelium increased significantly. Additionally, the positive expressions of FADD were significantly correlated with lymph node metastasis of SCCs and the 5-year diseasespecific survival rates. Thus, SCC cells with the expression of FADD are possibly more likely to become metastatic and to worsen survival rates. As previously mentioned, FADD is imperative for transmitting signals from cell surface receptors in both cell apoptosis and proliferation. Therefore, many past studies investigating FADD were confined to its function within the cytoplasm; however, recent studies have demonstrated that FADD is located in both the nucleus and the cytoplasm. In this study, the immunoreactivity pattern of FADD in oral SCCs clearly demonstrated a predominant nuclear localization pattern. As the function of FADD in the nucleus has not been clarified, a meaningful localization of FADD in the nucleus is currently under investigation. Less
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Report
(3 results)
Research Products
(7 results)
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[Journal Article] Roles of IL-6 and PTHrP in osteoclast formation associated with oral cancers: The significance of IL-6 synthesized by stromal cells in response to cancer cells.2010
Author(s)
Kayamori K, Sakamoto K, Nakashima T, Takayanagi H, Morita K, Omura K, Nguyen ST, Miki Y, Akashi T, Yamada-Okabe H, Ogata E, Yamaguchi A
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Journal Title
Am J Pathol. 176
Pages: 968-980
Related Report
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