NOX1 and NOX2: Two enzymes that promote endothelial-to-mesenchymal transition induced by melanoma conditioned media
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
35085755
DOI
10.1016/j.phrs.2022.106097
PII: S1043-6618(22)00042-1
Knihovny.cz E-zdroje
- Klíčová slova
- Endothelial cell, Endothelial-to-mesenchymal transition, Melanoma, NADPH oxidases, ROS,
- MeSH
- endoteliální buňky * MeSH
- epitelo-mezenchymální tranzice MeSH
- kultivační média speciální farmakologie MeSH
- lidé MeSH
- melanom * MeSH
- nádorové mikroprostředí MeSH
- proliferace buněk MeSH
- reaktivní formy kyslíku MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kultivační média speciální MeSH
- reaktivní formy kyslíku MeSH
Tumor microenvironment plays an important role in melanoma progression. Recent studies reported endothelial cells (EC) are involved in endothelial-to-mesenchymal transition (EndMT). During this phenotypic switch, EC progressively lose their endothelial markers and acquire mesenchymal properties. Depending on their concentration, reactive oxygen species (ROS) can control tumor growth. In EC, ROS are mainly produced by NAPDH oxidases (NOX) such as NOX1 and NOX2. The aim of the present study was to determine the role of these enzymes in EndMT induced by conditioned media (CM) from SK-MEL 28 melanoma cells. The capacity of CM to induce EndMT in HUVEC after 24 h, 48 h or 72 h has been evaluated by following endothelial HUVECs proliferation, migration and their capacity to form capillary on ECMgel®. Furthermore, EndMT was confirmed by western blot and flow cytometry. To determine the role of NOX in EndMT, specific NOX1 and/or NOX2 inhibitors has been tested. TGF-β2 + /- IL-1β was used as positive control. ROS production was determined through DCFDA assay. An altered endothelial phenotype was found in CM-treated HUVECs. This phenotypic modification was correlated with a decrease in both capillary formation on ECMgel® and cell proliferation and an increase in cell migration. Exposure to CM for 48 h significantly enhanced intracellular HUVECs ROS production and this increase was prevented by the dual pharmacological inhibition of NOX1 and NOX2. Furthermore, inhibition of NOX1/2 also leads to a partial reversion of CM-induced EndMT. These data confirmed the role of NOX1 and NOX2 in EndMT induced by melanoma cancer cell secretome.
CNRS ERL 7001 LNOx and EA7501 University of Tours Tours France
Department of Dermatology Angers University Hospital Angers France
PhyOS UMR 1238 Inserm Université de Nantes Nantes France
Team SOAP CRCINA UMR 1232 Inserm CNRS Université de Nantes Université d'Angers Nantes France
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