2004 Fiscal Year Final Research Report Summary
A new anti-cancer strategy by control ling crosstalk of oral carcinoma cells with extracellular matrix molecules
Project/Area Number |
14370581
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Morphological basic dentistry
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Research Institution | Niigata University |
Principal Investigator |
SAKU Takashi Niigata University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (40145264)
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Co-Investigator(Kenkyū-buntansha) |
CHENG Jun Niigata University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (40207460)
IDA Hircko Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (60293213)
OHSHIRO Kazufumi Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (50332648)
SUZUKI Makoto Niigata University, Medical and Dental Hospital, lecturer, 医歯学総合病院, 講師 (50107778)
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Project Period (FY) |
2002 – 2004
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Keywords | squamous cell carcinoma / tumor stroma / co-culture / extracellular matrix / interstitial cells / in-situ hybridization / RT-PCR / microdissection |
Research Abstract |
It was poorly understood which cell types, tumor cells or stromal cells, were responsible for the production of extracellular matrix (ECM) molecules in the neoplastic stroma. To investigate the role of each cell type's participation in the production of ECM molecules, as a primary experiment of this research project, the expression of four ECM molecules at the protein and the mRNA levels was studied in two kinds of co-culture systems in direct and indirect contacts between squamous cell carcinoma (SCC) cell systems and stromal fibroblast cell systems. While similar protein and mRNA expression levels for perlecan and other ECM molecules between SCC cells and fibroblasts in a monocellular culture condition, these ECM expression levels of fibroblasts were elevated, and instead those of SCC cells dropped when they were in contact with SCC cells. The differences in the levels between SCC cells and fibroblasts were significantly more evident in direct contact than in indirect contact. These results indicated that oral SCC cells produce ECM molecules in the absence of stromal fibroblasts, which correspond to carcinomas in-situ, and that they stop producing ECM in the presence of fibroblasts, which correspond to invasive SCC. These phenomena were also confirmed in tissue sections from oral carcinoma surgical specimens by immunohistochemistry and in-situ hybridization. In other experiments, ECM production and its metabolism were shown to be controlled by both parenchymal and stromal cells. It is thus suggested that stromal fibroblasts after direct contact with invading SCC cells are more responsible than SCC cells for the formation of neoplastic stroma, and that histological invasion of SCC can be defined as the presence of stromal induction. Based on the findings, we have proposed a tumor biological concept of "parenchymal-stromal switching for ECM production."
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Research Products
(24 results)
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[Journal Article] Nucleotide sequences and functions of the epstein-barr virus latent membrane protein 1 genes isolated from salivary gland lymphoepithelial carcinomas2005
Author(s)
Jen KY, Higuchi M, Cheng J, Li J, Wu LY, Li YF, Lin HL, Chen Z, Gurtsevitch V, Fujii M, Saku T
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Journal Title
Virus Genes 30(2)
Pages: 223-235
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of potential biomarkers of lymph node metastasis in oral squamous cell carcinoma by cDNA microarray analysis2003
Author(s)
Nagata M, Fujita H, Ida H, Hoshina H, Inoue T, Seki Y, Ohnishi M, Ohyama T, Shingaki S, Kaji M, Saku T, Takagi R
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Journal Title
International Journal of Cancer 106(5)
Pages: 683-689
Description
「研究成果報告書概要(欧文)」より