Dynamic changes of basement membrane molecules and degradation enzymes in stroma remodelled by proliferation and in asion of salivary gland carcinoma cells.

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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.