2026-07-23T18:45:34Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/66882024-09-27T09:25:11Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Mira, Emilia
author
Carmona-Rodriguez, Lorena
author
Perez-Villamil, Beatriz
author
Casas, Josefina
author
Fernández-Aceñero, María Jesús
author
Martinez-Rey, Diego
author
Martin-Gonzalez, Paula
author
Heras-Murillo, Ignacio
author
Paz-Cabezas, Mateo
author
Tardaguilal, Manuel
author
Oury, Tim D.
author
Martin-Puig, Silvia
author
Ana Lacalle, Rosa
author
Fabrias, Gemma
author
Diaz-Rubio, Eduardo
author
Manes, Santos
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
Fundación Domingo Martínez
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Asociación Española Contra el Cáncer
2018-11-22T08:10:53Z
2018-11-22T08:10:53Z
2018
Nat Commun. 2018; 9(1):575
10.1038/s41467-018-03079-1
2041-1723
Nature Communications
29422508
http://hdl.handle.net/20.500.12105/6688
One drawback of chemotherapy is poor drug delivery to tumor cells, due in part to hyper-permeability of the tumor vasculature. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme usually repressed in the tumor milieu. Here we show that specific SOD3 re-expression in tumor-associated endothelial cells (ECs) increases doxorubicin (Doxo) delivery into and chemotherapeutic effect on tumors. Enhanced SOD3 activity fostered perivascular nitric oxide accumulation and reduced vessel leakage by inducing vascular endothelial cadherin (VEC) transcription. SOD3 reduced HIF prolyl hydroxylase domain protein activity, which increased hypoxia-inducible factor-2 alpha (HIF-2 alpha) stability and enhanced its binding to a specific VEC promoter region. EC-specific HIF-2 alpha ablation prevented both the SOD3-mediated increase in VEC transcription and the enhanced Doxo effect. SOD3, VEC, and HIF-2 alpha levels correlated positively in primary colorectal cancers, which suggests a similar interconnection of these proteins in human malignancy.
eng
SOD3 improves the tumor response to chemotherapy by stabilizing endothelial HIF-2 alpha
journal article
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SOD3ImprovesTheTumor_2018.pdf
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SOD3ImprovesTheTumor_2018_MOESM1_ESM.pdf
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text/plain
SOD3ImprovesTheTumor_2018.pdf.txt
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https://repisalud.isciii.es/bitstreams/a1b62f19-6aff-4e01-9974-3d7c30eeb6a2/download
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SOD3ImprovesTheTumor_2018_MOESM1_ESM.pdf.txt