PLASMINOGEN ACTIVATORS PLAY AN ESSENTIAL ROLE IN EXTRACELLULAR-MATRIXINVASION BY LYMPHOBLASTIC T-CELLS

Involvement of extravascular sites, in particular infiltration of the central nervous system, is a frequent complication of T-lymphoblastic leukemia and contributes to leukemia-associated morbidity. In this rep ort, we studied the contribution of plasminogen activators to the inva sive properties of 7 human T-cell lines in a model of transmigration t hrough an extracellular matrix. The T-cell lines were found to express either urokinase (u-PA) and high levels of U-PA receptor or tissue-ty pe plasminogen activator (t-PA) and low levels of u-PA receptor. The r ate of transmigration was consistently higher for u-PA-expressing cell s than for t-PA-expressing cells. PA-inhibitor type 1 (PAI-1) was dete cted in the conditioned medium of one cell line and PAI-2 was detected in cell extracts from 6 lines. The transmigration of 6 out of 7 cell lines was inhibited by trasylol, an inhibitor of plasmin, by an excess of exogenous PAI-1 or PAI-2, and by antibodies to the particular PA t ype expressed by the cells. Partial inhibition of transmigration by th e amino-terminal fragment of u-PA implies that the u-PA receptor contr ibutes to transmigration. Thus, the transmigration of T-leukemia cells through a barrier of extracellular matrix requires PA-dependent prote olysis, which can be provided either by u-PA or t-PA. Specific inhibit ion of the PA system could provide a means to inhibit tissue invasion by T lymphoblastic cells. (C) 1997 Wiley-Liss, Inc.