| Project/Area Number |
10557170
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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 |
病態科学系歯学(含放射線系歯学)
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| Research Institution | NIIGATA UNIVERSITY |
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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) |
SUZUKI Makoto NIIGATA UNIVERSITY, University Dental Hospital, Lecture, 歯学部・付属病院, 講師 (50107778)
IDA Hiroko (YONEMOCHI Hiroko) NIIGATA UNIVERSITY, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (60293213)
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)
NAKAJIMA Motowo NIIGATA UNIVERSITY, Novartis Pharma, Tsukuba Institute, Manager, 癌研究グループ, マネジャー(研究職)
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)
木村 信 新潟大学, 歯学部, 助手 (80251825)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥9,600,000 (Direct Cost: ¥9,600,000)
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| Keywords | extracellular matrix / heparan sulfate proteoglycan / fibronectin / integrin / cell adhesion / focal adhesion kinase / ACC3 / anti-cancer strategy / スラミン / RT-PCR / 口腔癌 / RGDペプチド |
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| Research Abstract |
We have analyzed anti-cancer effect in a situation in which adhesion of oral carcinoma cells to extracellular matrices is inhibited. To this end, suramin, a polysulfonated naphthylurea, which has been used as an anti-trypanosoma reagent but has also known as an inhibitor of lysosomal heparanase, was used for inhibition of adhesion of oral carcinoma cells, such as ACC3 cells of human salivary adenoid cystic carcinoma origin.
ACC3 cells have been known to biosynthesize excessive amounts of extracellular matrix (ECM) molecules, especially basement membrane-associated molecules, such as heparan sulfate proteoglycan, HSPG/perlecan, and fibronectin. When ACCE cess were cultivated in the presence of 100 ;uM suramin, secretion of ECM molecules by ACC3 cells into the culture medium was enhanced. When 200 fM suramin was added, attachment of ACC3 cells to culture dishes reduced significantly. In the presence of suramin and RGD peptides, which are an ECM recoginition site of integrins, the attachme
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nt was two times more inhibited. Thus, it was suggested that suramin affected integrih-dependent cell adhesion. By day 7 of culture in the presence of suramin, ECM molecules were shed more prominently into the culture medium of ACC3 cells. Immunofluorescence showed that ECM molecules and integrins were localized within the cytoplasm but not in the extracellular space or in the cell surface. These results indicated suramin inhibited cell membrane assembly of integrin and consequently trapping of ECM molecules by cell surface integrins.
Immunoprecipitation and pulse-chase experi-ments showed that suramin inhibited biosynthesis of an unknown molecule with Mr. 120 kDa, which was co-precipitated with integrin a5. Immunoblotting experiments showed that the 120 kDa molecule was focal adhesion kinase (FAK), which functions in phospholylation of integrins. The results indicated that suramin inhibit FAK expression of ACC3 cells, which resulted in integrin function in cellular attachment.
These results clearly indicate that the inhibition of cell surface receptors for ECM molecules can be one of the strategies for suppression of oral carcinoma cell growth. Less
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