TY - JOUR A1 - Jüngel, Eva A1 - Krüger, Geraldine A1 - Rutz, Jochen A1 - Nelson, Karen A1 - Werner, Isabella A1 - Relja, Borna A1 - Seliger, Barbara A1 - Fißlthaler, Beate A1 - Fleming, Ingrid A1 - Tsaur, Igor A1 - Haferkamp, Axel A1 - Blaheta, Roman A. T1 - Renal cell carcinoma alters endothelial receptor expression responsible for leukocyte adhesion T2 - OncoTarget N2 - Renal cell carcinoma (RCC) escapes immune recognition. To elaborate the escape strategy the influence of RCC cells on endothelial receptor expression and endothelial leukocyte adhesion was evaluated. Human umbilical vein endothelial cells (HUVEC) were co-cultured with the RCC cell line, Caki-1, with and without tumor necrosis factor (TNF)-alpha. Intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial (E)-selectin, standard and variants (V) of CD44 were then analysed in HUVEC, using flow cytometry and Western blot analysis. To determine which components are responsible for HUVEC-Caki-1 interaction causing receptor alteration, Caki-1 membrane fragments versus cell culture supernatant were applied to HUVECS. Adhesion of peripheral blood lymphocytes (PBL) and polymorphonuclear neutrophils (PMN) to endothelium was evaluated by co-culture adhesion assays. Relevance of endothelial receptor expression for adhesion to endothelium was determined by receptor blockage. Co-culture of RCC and HUVECs resulted in a significant increase in endothelial ICAM-1, VCAM-1, E-selectin, CD44 V3 and V7 expression. Previous stimulation of HUVECs with TNF-alpha and co-cultivation with Caki-1 resulted in further elevation of endothelial CD44 V3 and V7 expression, whereas ICAM-1, VCAM-1 and E-selectin expression were significantly diminished. Since Caki-1 membrane fragments also caused these alterations, but cell culture supernatant did not, cell-cell contact may be responsible for this process. Blocking ICAM-1, VCAM-1, E-selectin or CD44 with respective antibodies led to a significant decrease in PBL and PMN adhesion to endothelium. Thus, exposing HUVEC to Caki-1 results in significant alteration of endothelial receptor expression and subsequent endothelial attachment of PBL and PMN. KW - adhesion KW - endothelial receptor expression KW - leukocytes KW - renal cell carcinoma KW - tumor immune escape Y1 - 2016 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45211 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-452115 SN - 1949-2553 N1 - This article has been corrected: OncoTarget, 8.2017, Nr. 1, S. 1953-1954, doi:10.18632/oncotarget.14438 N1 - All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. VL - 7 IS - 15 SP - 20410 EP - 20424 PB - Impact Journals LLC CY - [s. l.] ER -