A T-cell-related proteinase expressed by T-lymphoma cells activates their
endogenous pro-urokinase
G Brunner, U Vettel, S Jobstmann, MD Kramer and V Schirrmacher
German Cancer Research Center, Institute of Immunology and Genetics,
Heidelberg.
In this report, we investigated the expression and activation of
proteolytic enzymes by mouse T-lymphoma cell lines of differing metastatic
potential. In contrast to the low metastatic Eb line, the metastatic
variants ESb and ESb-MP secreted urokinase-type plasminogen activator
(u-PA), which was present in the culture supernatant predominantly in the
active form (ESb, 96%; ESb-MP, 80%). All three T- lymphoma variants
expressed a mainly cell surface-associated proteinase, which proved to be
immunologically and enzymatically related to the murine T-cell-associated
serine proteinase-1 (MTSP-1). Intact lymphoma cells were able to activate
the recombinant human proenzyme of u-PA (pro-u-PA) by a plasmin-independent
mechanism, because plasmin contamination of the cells was not detectable.
When ESb- MP cells were cultured in the presence of inhibitors of MTSP-1,
such as antithrombin III, Pro-Phe-Arg-chloromethylketone, or aprotinin, the
ratio of endogenously activated murine u-PA to inactive pro-u-PA in
conditioned medium was significantly reduced (from 80% to 15%). The most
potent inhibitor, antithrombin, did not inhibit plasmin-catalyzed pro-u-PA
activation. These results suggest a novel autocrine mechanism of
plasmin-independent pro-u-PA activation for metastatic T lymphomas by the
production of an MTSP-1-related proteinase. The ability to initiate the
proteolytic cascade of plasminogen activation in the absence of plasmin
might contribute to the metastatic behavior of these cells observed in
vivo.
Volume 79,
Issue 8,
pp. 2099-2106,
04/15/1992
Copyright © 1992 by The American Society of Hematology
