1995 Fiscal Year Final Research Report Summary
Study on invasion mechanism of oral cancer for therapeutic implication
| Project/Area Number |
06454532
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 | Kyushu University (1995)
Osaka University (1994) |
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Principal Investigator |
SHIRASUNA Kanemitsu Kyushu University Faculty of Dentistry, 2nd Department of Oral and Maxillofacial Surgery, Professor, 歯学部, 教授 (30093420)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Salivary gland tumor / Invasion / Extracellular matrix / Protease / Protease inhibitor / Matrix degradation / Motility |
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| Research Abstract |
In order to implicate in cancer therapy, I have been studying invasion mechanism of oral cancer using adenoid cystic carcinoma (ACC) cell lines and oral squamous cellcarcinoma (SCC) cell lines in vitro.
Invasion of oral-carcinoma cells in an in vitro model was found to be regulated by various factors, including epidermal growth factor (EGF), dexamethasone (DEX), factors from oral fibroblasts, and extracellular matrix. One of mechanisms is largely mediated by proteolytic activity of cancer cells. Our data showed a correlation between invasion and plasminogen activator ; e.g., EGF is potent stimulator and DEX is inhibitor. Fractionation of conditioned medium from fibroblasts demonstrated that it contains at least two factors which stimulate cell motility and proteolytic activity of oral-carcinoma cells. Purification of the motility factor suggested that it is a novel protein which stimulates cell motility via a signalling pathway mediated by a pertussis-toxin-sensitive G protein and tyrosine phosphorylation. ACC cells display the greatest response to this factor. Examination showed that basal lamina components including fibronectin, laminin, and type IV collagen stimulated motility of oral-carcinoma cells. ACC cells are more responsive than any SCC cells. The high motility response to these components and motility factor from fibroblasts seems to be one of characteristics of ACC cells that invade relentlessly into adjacent tissues including nerve and endothelial sheaths. Further study is required to understand why ACC cells are high responsive to these factors.
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