STIMULATION OF THE EXPRESSION AND THE ENZYME-ACTIVITY OF AMINOPEPTIDASE N CD13 AND DIPEPTIDYLPEPTIDASE IV/CD26 ON HUMAN RENAL-CELL CARCINOMA-CELLS AND RENAL TUBULAR EPITHELIAL-CELLS BY T-CELL-DERIVED CYTOKINES, SUCH AS IL-4 AND IL-13/

Aminopeptidase N (APN) and dipeptidylpeptidase IV (DPIV) are transmemb rane type II molecules widely distributed in mammalian tissues. In rec ent years, the interest in cell surface peptidases has increased consi derably because, among other things, several reports indicate roles of ectopeptidases in tumour cell metastasis. Investigations into the reg ulation of APN and DPIV on tumour cells are rare. We report, for the f irst time, that IL-4 and IL-13 can up-regulate protein expression as w ell as enzymatic activity of both the peptidases on renal carcinoma ce lls and renal tubular epithelial cells in culture. The analysis of mRN A by competitive polymerase chain reaction (PCR) confirmed our results with respect to the APN increase at the level of gene expression. IL- 1 beta and tumour necrosis factor-alpha (TNF-alpha) augmented the IL-4 -induced effect with respect to APN but not to DPIV. A 5-day incubatio n with interferon-gamma (IFN-gamma) increased protein expression, espe cially of APN and, to a lesser extent, also of DPIV, whereas no signif icant increase in enzymatic activity could be observed. Small concentr ations of transforming growth factor-beta 1 (TGF-beta 1) inhibit the e xpression and enzyme activity of DPIV. IL-6, IL-7, IL-10 and granulocy te-macrophage colony-stimulating factor (GM-CSF) have been found to be without any effect on APN and DPIV. For a prospective therapeutic reg imen with T cell-derived cytokines it has to be considered that-beside s their effect on tumour cell growth-cytokines might affect surface ec topeptidases involved in tumour cell adhesion processes. The inhibitio n of APN and DPIV could be a new approach to suppression of cancer spr ead.