Project/Area Number |
06454508
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
|
Allocation Type | Single-year Grants |
Research Field |
Morphological basic dentistry
|
Research Institution | Niigata University |
Principal Investigator |
SAKU Takashi Niigata University School of Dentistry ; Professor, 歯学部, 教授 (40145264)
|
Co-Investigator(Kenkyū-buntansha) |
ODA Kimimitsu Niigata University School of Dentistry ; Professor, 歯学部, 教授 (10122681)
KIMURA Shin Niigata University School of Dentistry ; Assistant Professor, 歯学部, 助手 (80251825)
CHENG Jun Niigata University School of Dentistry ; Assistant Professor, 歯学部, 助手 (40207460)
FUKUSHIMA Masahiro Niigata University School of Dentistry ; Associate Professor, 歯学部, 助教授 (00018631)
|
Project Period (FY) |
1994 – 1995
|
Project Status |
Completed (Fiscal Year 1995)
|
Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1995: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1994: ¥4,700,000 (Direct Cost: ¥4,700,000)
|
Keywords | Adenoid cystic carcinoma / ACC2 / ACC3 / Basement membrane / Confoal laser microscopy / Heparan sulfate proteoglycan / Heparanase / Collagenase |
Research Abstract |
The characteristic cribriform histology of adenoid cystic carcinoma (ACC) arising in the human salivary gland is caused by retention of basement membrane molecules (BMMs) in the pseudocystic space. However, it is unknown whether the characteristic stroma of ACC is produced by the parenchymal cells or by stromal cells. In this study, we determined biosynthesis of BMMs in the two human ACC cell systems, ACC2 and ACC3 immuno-histochemically and biochemically. Immunofluorescence for fibronectin and the four BMMs : type IV collagen, laminin, entactin and heparan sulfate proteoglycan (HSPG) first appeared diffusely in the cytoplasm, and they changed into aggregation of granules in the perinuclear area. With formation of colonies, these signals were present in the extracellular space and co-localized with heparanase and other enzymes. After the cells formed a confluent monolayr, extracellular signals started to decrease in the reverse proportion of reappearance of intracellular ones. When cultured in collagen gel, the cells formed spherical colonies with vacuolar structures containing BMMs. Such processes of biosynthesis and degradation of BMMs was confirmed by metabolic labeling, immunoprecipitation and fluorography for HSPG. The results indicated that the parenchymal cells of ACC synthesize the BMMs and fibronectin, secrete them into the extracellular milieu, and remodel the extracellular deposits. It is hence suggested that the characteristic stromal pseudocysts of ACC is resulted from their own secretion and enzymatic degradation of the BMMs and fibronectin by the tumor cells.
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