No abstract

Summary.-Using a fibrin-agarose-overlay technique, high levels of plasminogendependent fibrinolytic activity have been demonstrated in cell lines derived from an ethylnitrosourea-induced glioma of the rat brain. Cell lines derived from normal adult rat brain showed only low levels of activity. The degree of lysis produced by a cell line was dependent on the average number of cells per colony, and a different pattern of response was observed for tumour and normal cell lines. A good positive correlation existed between the level of fibrinolytic activity, growth in agar and tumourigenicity of a cell line. Fibrinolytic activity was associated with cell lines derived at various times in the latent period, before the appearance of a visible tumour. Many cell lines derived from rat brains at 57-60 (E7), 90-91 (E8) and 111-112 (E6) days after transplacental exposure to ethylnitrosourea showed fibrinolytic activity, and in the latter group the close association with growth in agar and tumourigenicity was also demonstrated. Results from cell lines derived in the E7 and E8 experiments indicated that the possession of fibrinolytic activity preceded the ability of cells to form colonies in agar.

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The production of plasminogen activator (PA) by two cloned cell lines, one from an ethylnitrosourea-induced glioma (A15A5) and the other from normal adult rat brain (ARBO C9), has been investigated. Three assays were used to detect and measure PA in harvest fluids, cells and cell lysates. Similar levels were detected in harvest fluids from both cell lines. However, the cell and lysate assays indicated much higher levels in the tumor line. When actively growing cells were compared A15A5 cells had approximately 16X more fibrinolytic activity than the control cells with a limit of detection in the order of 10(3) cells or 1 microgram protein (cell lysate). In contrast for the control cells PA could only be detected when upwards of 10(4) cells or 5-10 micrograms protein were assayed. Plaminogen activator in as few as 10(3) tumor cells could be detected in the presence of 10(4) non-tumor cells. Plasminogen activator in 26 micrograms protein of A15A5 cell lysate could also be detected in the presence of 44 micrograms protein from ARBO C9 lysates indicating no inhibitory activity in the control cell lysates. Levels of PA in both harvest fluids and cell lysates were determined as cultures progressed through the growth cycle. For cell lysates this showed a build-up of PA in the normal cell line as the cells approached and attained confluence. A much higher level was measured in the tumor cells soon after seeding and maintained to confluence. No differences in growth cycle-associated changes in secreted PA could be determined in harvest fluids: both cell lines showing similar levels at confluence.