Production of plasminogen activator inhibitor type-2 in human peripheral blood monocytes upregulated in vitro by the quinoline-3-carboxamide, Linomide

Abstract

Cumulative evidence suggests plasminogen activator inhibitor type-2 (PAI-2) has a tumor suppressive effect owing to its inhibition of urokinase-type plasminogen activator (u-PA) activity. One strategy for anti-tumor treatment might be to stimulate the endogenous production of PAI-2 by monocytes/macrophages. In the present study, human peripheral blood mononuclear cells (PBMC) were incubated with Linomide, a quinoline-3-carboxamide previously shown to exert anti-tumor effects in several animal models. We found Linomide to increase the antigen concentration and enhance the mRNA levels of PAI-2 in a dose-dependent way. In situ hybridization, performed to localize PAI-2 mRNA in PBMC, showed PAI-2 to be exclusively expressed in the monocyte population in which Linomide treatment induced enhanced mRNA expression. Stimulation of endogenous PAI-2 production might be a new approach in tumor therapy.