HORMONAL AND EXTRACELLULAR-MATRIX REGULATION OF PLASMINOGEN-ACTIVATORIN A BOVINE MAMMARY EPITHELIAL-CELL LINE

The effects of lactogenic hormones on urokinase plasminogen activator (u-PA) produced by bovine mammary epithelial cells (MAC-T) were examin ed. High levels of u-PA activity were detected in growth arrested cell s cultured on plastic. This suggests that high levels of PA activity a lone are not sufficient to induce proliferation of bovine mammary epit helial cells. Cells were cultured on various extracellular matrices: p lastic, fibronectin, collagen, matrigel, and laminin. Basal levels of u-PA activity in media from MAC-T cells cultured on matrigel were 1.6- , 2-, 2- and 3.5-fold higher than that of cells cultured on plastic, f ibronectin, collagen, and laminin, respectively. Insulin increased (P < 0.01) mammary epithelial u-PA activity on a per cell basis, an effec t observed irrespectively of the type of extracellular matrix onto whi ch cells were cultured. Not unexpectedly, insulin-like growth factor ( ICF)-I, Des(1-3) ICF-I and IGF-II increased mammary epithelial u-PA ac tivity on a per cell basis and u-PA mRNA levels, thus, mimicking the e ffect of insulin. Dexamethasone suppressed (P < 0.01) u-PA activity bu t was unable to suppress the insulin-induced increase in u-PA activity of cells cultured on various extracellular matrices. These data indic ate that u-PA activity is modulated by both lactogenic hormones and th e type of extracellular matrix.