title: Renal cell carcinoma alters endothelial receptor expression responsible for leukocyte adhesion.
abstract: 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.
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Juengel
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Krueger
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Rutz
authors.affiliation: Department of Vascular and Endovascular Surgery, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Nelson
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Werner
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Borna
authors.initials: B
authors.lastname: Relja
authors.affiliation: Institute for Medical Immunology, Medical Faculty, Martin Luther University, Halle, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
authors.affiliation: Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Fisslthaler
authors.affiliation: Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Fleming
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Tsaur
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haferkamp
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Blaheta
mesh_terms: D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D019040:E-Selectin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C497483:CD44 protein, human; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D018960:Hyaluronan Receptors; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
keywords: adhesion; endothelial receptor expression; leukocytes; renal cell carcinoma; tumor immune escape