The Influence of Cytokines on the Adhesion of Renal Cancer Cells to Endothelium

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Abstract
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 after stimulation with different cytokines that include expression of the vascular adhesion molecules endothelial leukocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1. Human umbilical vein endothelial cells (HUVEC) were used to determine the adhesion of the RCC lines CCF-RC1, 2 and 7 to endothelium. Expression of cell adhesion molecules (CAM) on HUVEC and RCC lines was measured with immunoflowcytometry. Stimulation of HUVEC with rIl-1 beta, rTNF-alpha, or PMA resulted in a time-dependent 1.4- to 2.9-fold increase of RCC adhesion to HUVEC. Significant increased tumor cell binding was observed after 4 hours and paralleled the time-dependent induction of ELAM-1 and VCAM-1. Immunocytometry demonstrated the presence of the ligands sialyl Lewis X and VLA-4 on RCC, and blocking studies with monoclonal antibodies 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. This 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.