Stromal remodeling in processes of proliferation, invasion and metastasis of oral carcinoma cells : a molecular pathological study

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We have analyzed the biosynthesis of extracellular matrix molecules, matrix degrading enzymes and receptors for the extracellular matrix (ECM) molecules in oral carcinoma cells in culture by indirect immunofluorescence, biochemical and molecular biological techniques. These oral carcinoma cells were shown to produce extracellular matrix molecules in vitro. The species and amounts of extracellular matrix molecules varied with carcinoma cells. Especially. amino acid compositions and glycosylation patterns of the molecules were distinct. The results suggested that these structural differences in extracellular matrix molecules determined biological characters of those cancer cells in vivo. ACC3 cells established from adenoid cystic carcinoma of the salivary gland, which were moderate in clinical course, as well as ZK-1 cells established from squamous cell carcinoma of tongue with low potential of metastasis synthesized larger amounts of heparan sulfate proteoglycan (HSPG). In contrast, MK-1 cells established from squamous cell carcinoma of tongue with high metastatic potency synthesized scarce amounts of HSPG and its receptor integrin (INT). Fibronectin (FN) was plentifully synthesized by ACC3 and MK-1 cells but not by ZK-I cells. In EN synthesized by ACC3 cells, both EDA and EDB regions were contained in their mRNAs, whereas MK-1 cells synthesized FN lacking those regions which were alternatively spliced-out. Among ECM degradative enzymes, plasmin was synthesized only by ACC3 cells and MMP9 in MK-1 cells. In MK-1 cells, N-linked oligosaccharides in INT alpha5, alpha2 and beta1 were 5 kDa larger than those of other cells. These results clearly indicated that the structures and metabolic processes of ECM molecules were important for cell adhesion onto the ECM and hence clinical phenotypes such as invasiveness and metastatic abilities of oral carcinoma cells.