PLASMIN INDUCES THE FORMATION OF MULTICELLULAR SPHEROIDS OF BREAST-CANCER CELLS

MCF7 and ZR75-1 breast cancer cells grow as adherent monolayers in tis sue culture. Treatment with the serum serine protease plasmin causes t hem to detach and to grow as floating multicellular spheroids. Two pla smin activators, urokinase plasminogen activator and streptokinase, in duce the same growth pattern changes in the presence of plasminogen. S erum contains also plasminogen activator inhibitors. Aged serum, defic ient in plasminogen activator inhibitors, converts spontaneously monol ayer boast cancer cells into multicellular spheroids which readily rev ert to monolayer growth after addition of fresh serum. Urokinase block s the reversion. The formation of multicellular spheroids does not aff ect the proliferative rate of breast tumor cells but endows tumor cell s with increased resistance to the chemotherapeutic drugs, doxorubicin and paclitaxel. (C) 1997 Elsevier Science Ireland Ltd.