Therapeutic approaches, including molecularly targeted therapies The inhibition of invasion and metastasis of oral cancers by molecularly targeted therapies Search for novel therapy and molecular pathogenesis of oral cancer metastasis
| Project/Area Number |
16390593
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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 | Kyushu University |
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Principal Investigator |
SHIRASUNA Kanemitsu Kyushu University, Graduate School Dental Science, Professor, 大学院歯学研究院, 教授 (30093420)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIURA Tuyoshi Kyushu University, Hospital, Research Associate, 大学病院, 助手 (40322292)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2006: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | Oral cancer / uPA / uPAR / integrin / tumor invasion / metastasis / VEGF / がん浸潤・転移 / 腺様嚢胞癌 / 細胞接着 / 転移モデル / リンパ管 / 細胞遊走 / 接着斑 |
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| Research Abstract |
The prognosis of patients with oral cancer is influenced by the presence of metastasis. Understanding the molecular pathogenesis of oral cancer metastasis may lead to a rational development of new therapies. The present study has demonstrated several molecules that could serve as targets for novel therapy. Although mechanism of metastasis remains unclear, tumor cells must migrate through the extracellular matrix (ECM) in order to invade local tissues and metastasize to distal sites. Migrating cells use both adhesion molecules and proteolytic enzymes to regulate their interaction with and response to ECM. One of the most important proteolysis systems is urokinase-type plasminogen activator (uPA)/ uPA receptor (uPAR)/plasmin. The expression levels of uPA and uPAR have been related to invasion and metastasis and a poor survival rate. uPA bound to uPAR exhibits enhanced proteolytic activity and directly activates plasminogen, matrix metalloproteases, which gives rise to enhanced ECM degrad
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ation. The uPA-uPAR interaction also mediates several signal events, regulates cell adhesion, modulates integrin activity, and triggers cell migration. The expression of uPA-uPAR is regulated by activation of AP-1 and NFκ-B, and inhibition of either AP-1 or NFκ-B with decoy system suppresses tumor invasion of oral cancer cells.
Adenoid cystic carcinoma (AdCC) is characterized by nerve and vascular invasion and frequent distant metastasis. Cell lines, such as ACCS, from AdCC have high surface level of uPAR and show high migration response to collagens, and this response is exclusively inhibited by the anti-a2 integrin antibody. On the collagens, AdCC form numerous focal adhesion consisting of uPAR, vincullin and paxillin. ACCS-AS cell line transfected with a vector expressing antisense uPAR RNA showed strong reduction of collagen-stimulated migration and focal adhesion assembly, suggesting that uPAR plays a key role in tumor invasion.
In addition, our study suggest that vascular endothelial growth factor (VEGF)-C and VEGF-D and the tetraspanin KAI-1/CD82 could serve as molecularly targeted therapy for oral cancer. Less
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] T-cell receptor V βgene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous cell carcinoma.2004
Author(s)
Kumamaru W, Nakamura S, Kadena T, Yamada A, Kawamura E., Sasaki M., Ooyama Y., Toyosima T., Hayashida J., Itoh K., Shirasuna K.
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Journal Title
International J. Cancer 108
Pages: 686-695
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] T-cell receptor V β gene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous cell carcinoma.2004
Author(s)
Kumamaru W, Nakamura S, Kadena T, Yamada A, Kawamura E, Sasaka M, Ohyama Y, Toyoshima T, Hayashida J, Itoh K, Shirasuna K.
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Journal Title
Int J Cancer 108
Pages: 686-695
Description
「研究成果報告書概要(欧文)」より
Related Report
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