| Project/Area Number |
13557178
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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 | 展開研究 |
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| Research Field |
Surgical dentistry
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| Research Institution | Ehime University |
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Principal Investigator |
HAMAKAWA Hiroyuki Ehime University School of Medicine, Department of Oral & Maxillofacial Surgery, professor, 医学部, 教授 (20127905)
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| Co-Investigator(Kenkyū-buntansha) |
TACHIKAWA Tetsuhiko Showa University, Dental School, Department of Oral pathology, Professor, 歯学部, 教授 (10085772)
SHINTANI Satoru Ehime University School of Medicine, Department of Oral & Maxillofacial Surgery, assistant professor, 医学部, 助教授 (80294429)
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| Project Period (FY) |
2001 – 2003
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| Keywords | oral cancer / GFP / micrometastasis / CXCR4 / SDF1 / Akt / PI3K / VEGF |
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| Research Abstract |
We established a stably transfected cell line which expresses high levels of green fluorescent protein (GFP), thus permitting the detection and visualization of developing tumors and lymph node metastases after injection into nude mice. Cells of the human oral squamous carcinoma cell line (SAS-L1) were transfected with an expression vector containing a CDNA encoding humanized GFP and the neomycin resistance gene. A clone with stable high-level expression of GFP was selected in vitro using G418. To study metastasis formation, GFP-expressing cells were injected orthotopically into the tongue of nude mice. The resultant tumor growth in the tongue and micrometastases in the lymph nodes could be visualized by GFP fluorescence. Therefore a useful model has been developed for the study of oral cancer, firstly to understand the metastatic process and secondly for the evaluation of potential treatments.
Second, we analyzed the expression of COX2 and checked the effect of COX2 inhibitor. The purpose of this study is to investigate the relationship between the radiation sensitivity and elevated level of COX-2. Radiation sensitivity of the eight oral SCC cell lines differed greatly in their response to radiation. Further, the level of the COX-2 expression correlated inversely with increased tumor radiation sensitivity. The similar significant association between the response to preoperative radiation therapy and COX-2 overexpression was observed in the oral SCC patients. In addition, treatment with a COX-2 selective inhibitor enhanced the radioresponse of HSC-2 cell, which constitutively expressed COX-2. These results suggested that COX-2 expression level correlates to radiation tolerance and the COX-2 selective inhibitor may be a potent enhancer for tumor radioresponse in oral SCC.
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