INTERLEUKIN-1 MODULATES GROWTH OF HUMAN RENAL-CARCINOMA CELLS IN-VITRO

We have investigated the influence of interleukin 1 (IL-1) on growth o f human renal carcinoma cells in vitro. Using a capillary soft-agar cl oning system, 18% of freshly explanted renal carcinomas were stimulate d to grow by IL-1 and 4% were inhibited. Subsequent experiments with e stablished renal cancer cell lines demonstrated that two out of four c ell lines (Caki-2, A-498) were sensitive to IL-1. [H-3]Thymidine incor poration as well as monolayer growth was enhanced in Caki-2 cells in t he presence of high (10%) and low (1%) serum concentrations. Although clonogenic growth of A-498 cells was stimulated by IL-1, overall [H-3] thymidine incorporation and monolayer proliferation were decreased. Us ing radioligand experiments, 250 cell-surface receptors of high affini ty (K-D 4.5 x 10(-11) M) and 2500 receptors of low affinity (K-D 1.3 x 10(-9) M) were detected on A-498 cells. IL-1 binding was reduced unde r the influence of IL-1. Competition experiments with inhibiting antib odies against IL-1 receptor type I and type II revealed that signal tr ansduction was performed via type I receptors. After cross-linking to IL-1, receptor type I was immunoprecipitated using anti-IL-1 antibodie s. We hypothesise that, since IL-1 modulates in vitro growth of a subg roup of human renal cancer cells, interference with its mechanism of a ction may be of potential value in order to modulate tumour proliferat ion.