Premium
Plasminogen activators play an essential role in extracellular‐matrix invasion by lymphoblastic T cells
Author(s) -
Reiter Lars S.,
Spertini Olivier,
Kruithof Egbert K.O.
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970207)70:4<461::aid-ijc14>3.0.co;2-i
Subject(s) - plasminogen activator , extracellular matrix , cell culture , biology , plasmin , microbiology and biotechnology , receptor , extracellular , urokinase receptor , urokinase , t plasminogen activator , cancer research , endocrinology , biochemistry , genetics , enzyme
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 report, we studied the contribution of plasminogen activators to the invasive properties of 7 human T‐cell lines in a model of transmigration through an extracellular matrix. The T‐cell lines were found to express either urokinase (u‐PA) and high levels of u‐PA receptor or tissue‐type plasminogen activator (t‐PA) and low levels of u‐PA receptor. The rate of transmigration was consistently higher for u‐PA‐expressing cells than for t‐PA‐expressing cells. PA‐inhibitor type I (PAI‐1) was detected 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 type expressed by the cells. Partial inhibition of transmigration by the amino‐terminal fragment of u‐PA implies that the u‐PA receptor contributes to transmigration. Thus, the transmigration of T‐leukemia cells through a barrier of extracellular matrix requires PA‐dependent proteolysis, which can be provided either by u‐PA or t‐PA. Specific inhibition of the PA system could provide a means to inhibit tissue invasion by T lymphoblastic cells. Int. J. Cancer, 70:461–466, 1997. © 1997 Wiley‐Liss, Inc.