Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2017; 8(1):1953-54.

Renal cell carcinoma alters endothelial receptor expression responsible for leukocyte adhesion

Eva Juengel _, Geraldine Krueger, Jochen Rutz, Karen Nelson, Isabella Werner, Borna Relja, Barbara Seliger, Beate Fisslthaler, Ingrid Fleming, Igor Tsaur, Axel Haferkamp and Roman A. Blaheta

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Oncotarget. 2016; 7:20410-20424. https://doi.org/10.18632/oncotarget.7804

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Abstract

Eva Juengel1, Geraldine Krueger1, Jochen Rutz1, Karen Nelson2, Isabella Werner3, Borna Relja4, Barbara Seliger5, Beate Fisslthaler6, Ingrid Fleming6, Igor Tsaur1, Axel Haferkamp1,*, Roman A. Blaheta1,*

1Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany

2Department of Vascular and Endovascular Surgery, Goethe-University Hospital, Frankfurt am Main, Germany

3Department of Thoracic, Cardiac and Vascular Surgery, Goethe-University Hospital, Frankfurt am Main, Germany

4Department of Trauma, Hand and Reconstructive Surgery, Goethe-University Hospital, Frankfurt am Main, Germany

5Institute for Medical Immunology, Medical Faculty, Martin Luther University, Halle, Germany

6Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe-University, Frankfurt am Main, Germany

*Contributed equally as senior authors

Correspondence to:

Eva Juengel, e-mail: [email protected]

Keywords: adhesion, endothelial receptor expression, leukocytes, renal cell carcinoma, tumor immune escape

Received: July 22, 2015    Accepted: February 16, 2016    Published: March 01, 2016

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.


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