System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Epublish 5 citations

PubMed: 35267534 DOI: 10.3390/cancers14051226

Superoxide Dismutase-3 Downregulates Laminin α5 Expression in Tumor Endothelial Cells via the Inhibition of Nuclear Factor Kappa B Signaling.

Cancers (Basel) 14(5)

Authors: Lorena Carmona-Rodríguez, Diego Martínez-Rey, Paula Martín-González, Mónica Franch, Lydia Sorokin, Emilia Mira, Santos Mañes

Affiliations

  • Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB/CSIC), 28049 Madrid, Spain.
  • Bioinformatics Unit, Centro Nacional de Biotecnología (CNB/CSIC), 28049 Madrid, Spain.
  • Institute of Physiological Chemistry and Pathobiochemistry and Cells in Motion Interfaculty Centre, University of Münster, 48049 Münster, Germany.

Abstract

The balance between laminin isoforms containing the α5 or the α4 chain in the endothelial basement membrane determines the site of leukocyte diapedesis under inflammatory conditions. Extracellular superoxide dismutase (SOD3) induces laminin α4 expression in tumor blood vessels, which is associated with enhanced intratumor T cell infiltration in primary human cancers. We show now that SOD3 overexpression in neoplastic and endothelial cells (ECs) reduces laminin α5 in tumor blood vessels. SOD3 represses the laminin α5 gene (), but expression is not changed in SOD1-overexpressing cells. Transcriptomic analyses revealed SOD3 overexpression to change the transcription of 1682 genes in ECs, with the canonical and non-canonical NF-κB pathways as the major SOD3 targets. Indeed, SOD3 reduced the transcription of well-known NF-κB target genes as well as NF-κB-driven promoter activity in ECs stimulated with tumor necrosis factor (TNF)-α, an NF-κB signaling inducer. SOD3 inhibited the phosphorylation and degradation of IκBα (nuclear factor of the kappa light polypeptide gene enhancer in B-cells inhibitor alpha), an NF-κB inhibitor. Finally, TNF-α was found to be a transcriptional activator of but not of ; induction was prevented by SOD3. In conclusion, SOD3 is a major regulator of laminin balance in the basement membrane of tumor ECs, with potential implications for immune cell infiltration into tumors.

MeSH

Endothelium, Oxidative Stress, Blood Vessels, Membranes, Immunotherapy, Neoplasms, Basement Membrane, Superoxide Dismutase, T-Lymphocytes, Genes, Superoxides, B-Lymphocytes, Laminin, Endothelial Cells, Nf-Kappa B

Cited by