Interleukin 1 modulates growth of human renal carcinoma cells in vitro

We have investigated the influence of interleukin 1 (IL-1) on growth of human renal carcinoma cells in vitro. Using a capillary soft-agar cloning system, 18% of freshly explanted renal carcinomas were stimulated to grow by IL-1 and 4% were inhibited. Subsequent experiments with established renal cancer cell lines demonstrated that two out of four cell lines (Caki-2, A-498) were sensitive to IL-1. [3H]Thymidine incorporation as well as monolayer growth was enhanced in Caki-2 cells in the presence of high (10%) and low (1%) serum concentrations. Although clonogenic growth of A-498 cells was stimulated by IL-1, overall [3H]thymidine incorporation and monolayer proliferation were decreased. Using radioligand experiments, 250 cell-surface receptors of high affinity (KD 4.5 x 10(-11) M) and 2500 receptors of low affinity (KD 1.3 x 10(-9) M) were detected on A-498 cells. IL-1 binding was reduced under the influence of IL-1. Competition experiments with inhibiting antibodies against IL-1 receptor type I and type II revealed that signal transduction was performed via type I receptors. After cross-linking to IL-1, receptor type I was immunoprecipitated using anti-IL-1 antibodies. We hypothesise that, since IL-1 modulates in vitro growth of a subgroup of human renal cancer cells, interference with its mechanism of action may be of potential value in order to modulate tumour proliferation.