MODIFICATION OF INVASION AND DIFFERENTIATION IN HUMAN-MELANOMA CELL CLONES

In an attempt to define the role of plasminogen activator in invasiven ess and differentiation of human melanoma cells, the modulation of the se parameters was studied in two melanoma clones characterized by mark ed differences in their basal features, using 12-O-tetradecanoyl-phorb ol-13-acetate (TPA) and retinoic acid, two differentiation inducers, a nd doxorubicin, a cytotoxic agent. TPA induced only slight reductions, whereas retinoic acid and doxorubicin caused an increase in invasiven ess, enzymatic activity and differentiation in the clone showing low i nvasivity, low urokinase-type plasminogen activator levels and high di fferentiation. In contrast, in the clone showing high invasivity, high urokinase-type plasminogen activator levels and low differentiation i t was found that: TPA was ineffective; retinoic acid induced a reducti on of plasminogen activator but no modifications of invasiveness and d ifferentiation; doxorubicin caused a decrease in invasiveness and plas minogen activator activity but no modification of morphological featur es. The different behaviour of the two clones thus could be related to the basal features of the clones. The results reported here indicate that in the presence of these drugs the associations between invasiven ess and urokinase-type plasminogen activator activity and between inva siveness and differentiation are lost. Drug treatment therefore signif icantly affected the features of the clone characterized by low biolog ical aggressiveness (high differentiation, low invasiveness), whereas the highly aggressive clone did not show a consistent response to drug treatment.