[Are lysosomal enzymes involved in regulation of cell proliferation? (AUTHOR'S TRANSL)]

An activation of cell growth is affected by the addition of proteolytic enzymes to cultures of normal cells. A stimulation of integration of thymidine or guanosine into the nucleic acids, and a phosphorylation of histones resulted after protease treatment of cells and also of resulted after protease treatment of cells and also of isolated nuclei. Proteases are present in the lysosomes, among them also some whose maximal activity is in the region of pH 7. Lysosome preparations cause a stimulation of incorporation of nucleotides into the nucleic acids of cells in vitro and an increase in proliferation. It has been possible to demonstrate that the blastic transformation of lymphocytes can be activated by proteolytic enzymes, and that various inhibitors of proteolytic enzymes can check the activation, independent of the kind of blastogenic factor used. All blastogenic factors seem to produce an extrusion of lysosomal enzymes. Various authors reported an inhibition of lymphocyte-transformation by substances which stabilize the membrane of lysosomes. During the past 50 years reports were repeatedly published stating that malignant tumors yield proteolytic enzymes, which also may induce fibrinolysis. An increasing number of publications have recently been reported about the emission of a plasminogen-activating factor originating from virally transformed cells. Although the dependence of this effect on virus-infections could not be confirmed in all cases, it seems to be established that malignant or transformed cells release considerably more enzymes out of the lysosomes into the plasma and into the surrounding fluid than the corresponding normal cells. One should take into consideration that leakage of lysosomal membranes could be one of the causes of the increased proliferation of the majority of malignant cells.