THE INFLUENCE OF CYTOKINES ON THE ADHESION OF RENAL-CANCER CELLS TO ENDOTHELIUM

Purpose: The development of tumor metastasis requires direct adhesive interactions between tumor cells and vascular endothelium. We examined the adherence of renal cell carcinoma (RCC) lines to endothelium afte r stimulation with different cytokines that induce expression of the v ascular adhesion molecules endothelial leukocyte adhesion molecule (EL AM)-1, vascular cell adhesion molecule (VCAM)-1 and intercellular adhe sion molecule (ICAM)-1. Materials and Methods: Human umbilical vein en dothelial cells (HUVEC) were used to determine the adhesion of the RCC lines CCF-RC1, 2 and 7 to endothelium. Expression of cell adhesion mo lecules (CAM) on HUVEC and RCC lines was measured with immunoflowcytom etry. Results: Stimulation of HUVEC with rIl-1 beta, rTNF-alpha, or PM A resulted in a time-dependent 1.4- to 2.9-fold increase of RCC adhesi on to HUVEC. Significant increased tumor cell binding was observed aft er 4 hours and paralleled the time-dependent induction of ELAM-1 and V CAM-1. Immunocytometry demonstrated the presence of the ligands sialyl Lewis X and VLA-4 on RCC, and blocking studies with monoclonal antibo dies directed against tumor cell-endothelial interactions mediated by VCAM-1/VLA-4 and ELAM-1/sialyl Lewis X demonstrated marked inhibition of tumor cell adherence to cytokine-stimulated HUVEC. Conclusions: Thi s study demonstrates that cytokine-induced increases in RCC adherence to HUVEC are mediated in part by VCAM-1/VLA-4 and ELAM-1/sialyl Lewis X interactions and suggest that these molecules may play an important role in the ability of RCC to metastasize.