2004 Fiscal Year Final Research Report Summary
Search for Molecular Targets by Proteome Analysis and Its Use to Taylored-Made Therapy against Oral Cancer
| Project/Area Number |
15390615
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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 | HIROSHIMA UNIVERSITY |
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Principal Investigator |
OKAMOTO Tetsuji Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (00169153)
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| Co-Investigator(Kenkyū-buntansha) |
TORATANI Shigeaki Hiroshima University, Hospital, Instructor, 病院・講師 (90172220)
HAYASHIDO Yasutaka Hiroshima University, Hospital, Instructor, 病院・講師 (70243251)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Oral Squamous Cell Carcinoma / Single Nucleotide Polymorphism / Proteome analysis / NK cell activity / MICA molecule / Oral Cancer Susceptibility / LAK cell activity / Salivary Gland Tumor |
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| Research Abstract |
By two-dimensional PAGE and MALDI-TOFMS analysis, we have found that a major histocompatibility complex class I chain-related molecule A (MICA) protein, the ligand of NKG2D which is activation receptor on the most NK cells, LAK cells, and cytotoxic T cells, was specifically induced by vitamin A in oral cancer cell lines. RT-PCR and FACS analysis revealed that vitamin A derivative such as ATRA induced mRNA and protein expression of MICA in oral cancer cell lines, respectively.
We analysed MICA polymorphism (GCT triplet repeat polymorphism in the transmembrane domain) in 100 cases with Oral Squamous Cell Carcinoma(OSCC), and 103 randomly selected unrelated controls by direct sequencing and fragment analysis. Five distinct MICA polymorphisms were studied.
As a result, we have found that the percentage of the patient who has MICA 5.1 phenotype among total oral cancer patients is 30%, but that of control is 15% (X^2=16.203,P value=0.00006). NK activity of the patient of 5.1 allele is lower than that of the others of other alleles. By flow-cytometric analysis, MICA protein on the cell surface was detected in all cell lines. It has been reported that tumors have ways of evading the body's immune system. As one of the system of these, there are soluble forms of MICA (sMICA) in the serum. We have examined sMICA in the serum of 45 OSCC patients by ELISA. We have found the sMICA levels in OSCC patients were significantly higher than those in controls. On the other hand, sMICA serum concentration strongly correlated with the clinical state of OSCC patients and might serve as a novel biomarker of OSCC.
These results suggest that the susceptibility to OSCC is closely linked to the MICA microsatellite polymorphism and 5.1 allele might confer the risk of OSCC, and that serum levels of sMICA may serve as a novel molecular target/biomarker of OSCC for its diagnosis, therapy, and prognosis.
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