The biosynthesis of basement membrane molecules and fibronectin was studied in vitro in the two different human cell systems (ACC2 and ACC3) established from adenoid cystic carcinomas (ACC) of the salivary gland using immunofluorescence and confocal microscopy. When cells were attached and spread on dishes, fine granular immunofluorescence for type IV collagen, laminin, heparan sulphate proteoglycan, entactin, and fibronectin first appeared diffusely in the cytoplasm, and then changed in aggregation of coarse granules in the perinuclear area. With formation of colonies, these signals were present in the extracellular space, initially in the basal aspect of attached cells and consequently in the lateral intercellular space. After the cells formed a confluent monolayer, extracellular signals started to decrease in inverse proportion to the reappearance of intracellular ones. The results indicate that the parenchymal cells of ACC synthesize these five extracellular matrix molecules, secrete them into the extracellular milieu and remodel the extracellular deposits. It is suggested that the characteristic stromal architecture of ACC, represented by stromal pseudocysts, results from their own secretion of the basement membrane molecules and fibronectin.
An autopsied case of an 80‐year‐old man with spindle cell carcinoma of the gingiva is reported. The tumor was polypoid and mostly composed of a sarcomatous proliferation of spindle cells with a small focus of squamous cell carcinoma at the stalk portion. The carcinoma metastasized to a cervical lymph node, lungs and pleura with extension to the diaphragm. In the metastatic lymph node, the squamous cell component was more prominent than the spindle cell one, while only anaplastic pleomorphic carcinoma cells were found in the lungs. The spindle or anaplastic cells were immunohistochemically positive for vimentin and carci‐noembryonic antigen (CEA) but not for other epithelial antigens. We have concluded that the sarcomatoid component arose from the oral squamous cell carcinoma by a metaplastic process. This is the first case report of an oral spindle cell carcinoma examined by autopsy.
In order to reconstruct the characteristic three-dimensional architecture of adenoid cystic carcinoma, we cultured ACC2 cells, a cell system established from a human adenoid cystic carcinoma of the palate, in collagen gel matrix and transplanted them in SCID mice. In the collagen gel culture, the cells formed spherical colonies measuring 75.6 +/- 14.6 microns in diameter by 6 days after seeding. The tumor cell nests contained vacuolar structures that were immunopositive for heparan sulfate proteoglycan, type III collagen, type IV collagen, and fibronectin. The rim of the nests was argyrophilic and immunopositive for type I collagen, type IV collagen, laminin, and fibronectin. Transplants of ACC2 cells in SCID mice grew to form tumor masses in which pseudocysts were formed. The results indicate that our collagen gel culture system provides physiological conditions for ACC2 cells to secrete particular extracellular matrix molecules and form pseudocystic spaces.
ACC3, a human adenoid cystic carcinoma cell system of salivary gland origin, is able to synthesize and secrete a large amount of basement membrane molecules in vitro. To define the ultrastructural secreting pathway of these molecules, we immunolocalized heparan sulphate proteoglycan (HSPG) in ACC3 for 7 days of culture. In the early stage of culture, the main compartments immunolabelled were rough endoplasmic reticulum (rER) and small secretory vesicles. From days 3 to 4 after plating, it was noticed that HSPG was localized in partially dilated spaces of the perinuclear, rER and Golgi cisternae and in lysosomes or those fused with multivesicular bodies and endosomes. On and after day 5, almost every Golgi apparatus showed marked dilatation of the cisternae and HSPG was immunolocalized in these dilated spaces. In the later stage of culture, autophagic vacuoles or secondary lysosomes, which were simultaneously labelled for HSPG and cathepsin D, were accumulated in the cytoplasm. HSPG deposition in the intercellular space was clearly demonstrated from day 1 and increased during the culture. The results indicate that ACC3 cells have an enhanced turnover cycle for HSPG: not only its biosynthesis but also degradation of both endogenous or exogenous HSPG. Such intracellular events may be reflected in the characteristic histology and biological behaviour of adenoid cystic carcinomas.
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