THE EXPRESSION OF INVASIVE BEHAVIOR OF DIFFERENTIATED SQUAMOUS CARCINOMA CELL-LINE EVALUATED BY AN INVITRO INVASION MODEL

In order to elucidate the factors contributory to the expression of in vasiveness of oral squamous cell carcinoma, we conducted biochemical a nd morphological comparisons of well differentiated squamous carcinoma cell line OSC-19 (oral squamous cell carcinoma) and undifferentiated carcinoma cell line KB, both cultured on 3T3 cell-embedded collagen ge l (in vitro invasion model). OSC-19 cells invaded 3T3 cell-embedded co llagen gel, while KB celts and OSC-19 cells on 3T3 cell-free gel matri x were less invasive. Cultured OSC-19 cells were characterized by lowe r proliferating activity, lower secretion of laminin and higher secret ion of fibronectin than those of KB cells. Although the basement membr ane with deposition of laminin and type IV collagen was formed, it was discontinuous at the invasion front. Gelatin zymography and western b lotting showed matrix metalloproteinases (MMP), i.e., 72 kDa gelatinas e (MMP-2) and 92 kDa gelatinase (MMP-9). Gelatinolytic activity was as sayed, and was higher in OSC-19 cells than in KB cells or OSC-19 cells of the 3T3 cell-free model. By immunohistochemical analysis, MMP-2-po sitive cells were found scattered in both cell lines without any prefe rential localization, and the positivity for MMP-9 was localized in th e invasion front of OSC-19 cells. These results strongly suggest that the invasiveness of squamous cell carcinoma is well correlated with ce ll-matrix adhesion by fibronectin and with focal elaboration of metall oproteinases, especially MMP-9, which play a major role in degrading t he extracellular matrix components.