Plasminogen activation transforms the morphology of quiescent 3T3 cell monolayers and initiates growth

Plasminogen activator of cell origin converts the plasma protein plasminogen to the proteolytic enzyme plasmin. Recently, high levels of activator have been observed to be particularly associated with tumours and transformed cells, and a functional relationship between plasminogen activation and malignancy has been proposed. In this paper we have attempted to induce transformation-like morphology and growth in a population of confluent quiescent cells in tissue culture, by inducing plasminogen activation. Untransformed 3T3 cells grown to confluence in plasminogen-free medium were subjected to plasminogen activation by the addition of urokinase and plasminogen or plasminogen-containing acid-treated serum, or plasmin. Under these conditions, the previously well ordered monolayers became disrupted, with multilayering, and discontinuities in the cell sheet, and the cells simultaneously grew to significantly higher densities. Removal of the plasmin-containing medium supplements effected some restoration of normal morphology. Thus, lhen plasmin was present 3T3 cells did not become transformed, but expresses transformation-like features. Well ordered monolayer morphology and quiescence in 3T3 cells at confluence are therefore dependent upon the absence of plasminogen activation.