VHL promotes immune response against renal cell carcinoma via NF-κB-dependent regulation of VCAM-1

Vascular cell adhesion molecule 1 (VCAM-1) is an adhesion molecule assigned to the activated endothelium mediating immune cells adhesion and extravasation. However, its expression in renal carcinomas inversely correlates with tumor malignancy. Our experiments in clear cell renal cell carcinoma (ccRC...

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Bibliographic Details
Published in:The Journal of cell biology 2017-03, Vol.216 (3), p.835-847
Main Authors: Labrousse-Arias, David, Martínez-Alonso, Emma, Corral-Escariz, María, Bienes-Martínez, Raquel, Berridy, Jaime, Serrano-Oviedo, Leticia, Conde, Elisa, García-Bermejo, María-Laura, Giménez-Bachs, José M, Salinas-Sánchez, Antonio S, Sánchez-Prieto, Ricardo, Yao, Masahiro, Lasa, Marina, Calzada, María J
Format: Article
Language:English
Subjects:
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - immunology
Biomarkers, Tumor - genetics
Biomarkers, Tumor - immunology
Carcinoma, Renal Cell - genetics
Carcinoma, Renal Cell - immunology
Cell Line, Tumor
Gene Expression Regulation, Neoplastic - genetics
Gene Expression Regulation, Neoplastic - immunology
Humans
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Hypoxia-Inducible Factor 1, alpha Subunit - immunology
Integrin alpha4beta1 - genetics
Integrin alpha4beta1 - immunology
Kidney Neoplasms - genetics
Kidney Neoplasms - immunology
Mutation - genetics
Mutation - immunology
NF-kappa B - genetics
NF-kappa B - immunology
Signal Transduction - genetics
Signal Transduction - immunology
Transcription, Genetic - genetics
Transcription, Genetic - immunology
Vascular Cell Adhesion Molecule-1 - genetics
Vascular Cell Adhesion Molecule-1 - immunology
von Hippel-Lindau Disease - genetics
von Hippel-Lindau Disease - immunology
Von Hippel-Lindau Tumor Suppressor Protein - genetics
Von Hippel-Lindau Tumor Suppressor Protein - immunology
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Summary:Vascular cell adhesion molecule 1 (VCAM-1) is an adhesion molecule assigned to the activated endothelium mediating immune cells adhesion and extravasation. However, its expression in renal carcinomas inversely correlates with tumor malignancy. Our experiments in clear cell renal cell carcinoma (ccRCC) cell lines demonstrated that von Hippel Lindau (VHL) loss, hypoxia, or PHD (for prolyl hydroxylase domain-containing proteins) inactivation decreased VCAM-1 levels through a transcriptional mechanism that was independent of the hypoxia-inducible factor and dependent on the nuclear factor κB signaling pathway. Conversely, VHL expression leads to high VCAM-1 levels in ccRCC, which in turn leads to better outcomes, possibly by favoring antitumor immunity through VCAM-1 interaction with the α4β1 integrin expressed in immune cells. Remarkably, in ccRCC human samples with VHL nonmissense mutations, we observed a negative correlation between VCAM-1 levels and ccRCC stage, microvascular invasion, and symptom presentation, pointing out the clinical value of VCAM-1 levels as a marker of ccRCC progression.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201608024