INTERFERON INDUCES THYMIDINE PHOSPHORYLASE PLATELET-DERIVED ENDOTHELIAL-CELL GROWTH-FACTOR EXPRESSION IN-VIVO/

The enzyme/cytokine thymidine phosphorylase/platelet-derived endotheli al cell growth factor (TP/PD-ECGF) has diverse functions within cells, including the regulation of steady state thymidine levels, the conver sion of the cancer chemotherapeutic agent 5-fluorouracil (FUra) to an active metabolite, and the mediation of angiogenesis in normal and mal ignant cells, Although the levels of TP/PD-ECGF vary substantially amo ng different tissues and are generally found to be elevated in tumors, little is known about the control of its expression in vivo in humans , In this study, peripheral blood mononuclear cells were obtained from patients prior to and during treatment with IFN and FUra and analysed for TP/PD-ECGF expression, Sixteen of 21 patients (76%) exhibited an average 3-4-fold increase of TP/PD-ECGF protein levels after treatment with either IFN-alpha or -beta, with the remaining patients having ei ther a decrease (four patients) or no change (one patient) at the samp ling times examined, Expression in vivo increased rapidly within 1-2 h of IFN treatment and remained elevated for up to 48 h after its admin istration, The increase in TP/PD-ECGF protein was accompanied by a con comitant increase in TP/PD-ECGF mRNA levels, TP/PD-ECGF mRNA expressio n in cells in vitro was induced by IFN but not by pharmacologically re levant concentrations of FUra, suggesting that the IFN was responsible for the induction seen in the patients, This study demonstrates that IFN induces TP/PD-ECGF expression in vivo by regulation of the level o f mRNA expression.