Plasminogen activators play an essential role in extracellular-matrix invasion 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 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 1 (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.
Reiter
L S
LS
Department of Medicine, University Hospital Lausanne, Switzerland.
Spertini
O
O
Kruithof
E K
EK
D015703:Antigens, CD / Q000378:metabolism; D006801:Humans; D015458:Leukemia, T-Cell / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology*; D010960:Plasminogen Activators / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000502:physiology; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology
D015703:Antigens, CD; D009363:Neoplasm Proteins; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator