Plasminogen activators play an essential role in extracellular-matrix invasion by lymphoblastic T cells.
Int J Cancer
; 70(4): 461-6, 1997 Feb 07.
Article
en En
| MEDLINE
| ID: mdl-9033655
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Activadores Plasminogénicos
/
Leucemia de Células T
/
Invasividad Neoplásica
/
Proteínas de Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Int J Cancer
Año:
1997
Tipo del documento:
Article
País de afiliación:
Suiza
Pais de publicación:
Estados Unidos