STIMULATION OF TIMP-1 AND METALLOPROTEINASE PRODUCTION IN COCULTURES OF HUMAN TUMOR-CELLS AND HUMAN FIBROBLASTS

The co-cultures of five different human tumor cell lines with human no rmal fibroblasts significantly stimulated the production of tissue inh ibitors of metalloproteinases-1 (TIMP-1) when compared to cultures of individual cells. In the co-culture of T24 human urinary bladder carci noma cells and CCD 18 human fibroblasts, production of both TIMP-1 and metalloproteinases was stimulated, and the stimulatory effects were d ependent on the cellular ratio between the fibroblasts and carcinoma c ells. On day 6 of culture, collagenase and stromelysin were stimulated at a ratio of CCD 18 fibroblasts to T24 cells of 1:0.1, while the max imum TIMP-1 production occurred at a ratio of 1:1. Thus, the cellular ratio in the interaction of carcinoma cells with host fibroblasts affe cts the production of TIMP-1 and metalloproteinases and hence modulate s the balance between them.