Reactive oxygen species activation of MAPK pathway results in VEGF upregulation as an undesired irradiation response

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RESEARCH PRODUCT

Reactive oxygen species activation of MAPK pathway results in VEGF upregulation as an undesired irradiation response

Juergen Brieger Annette Affolter Martynas Drigotas Wolf J. Mann

subject

Vascular Endothelial Growth Factor A MAPK/ERK pathway Cancer Research Pathology medicine.medical_specialty MAP Kinase Signaling System Blotting Western Enzyme-Linked Immunosorbent Assay Biology Radiation Tolerance Pathology and Forensic Medicine chemistry.chemical_compound Downregulation and upregulation Cell Line Tumor Nitriles Butadienes medicine Humans Enzyme Inhibitors Extracellular Signal-Regulated MAP Kinases Protein kinase A chemistry.chemical_classification Reactive oxygen species Hydrogen Peroxide Immunohistochemistry Cytoprotection Up-Regulation Vascular endothelial growth factor Vascular endothelial growth factor A Otorhinolaryngology chemistry Cytoprotection Carcinoma Squamous Cell Cancer research Periodontics Electrophoresis Polyacrylamide Gel Oral Surgery Reactive Oxygen Species Intracellular

description

Background Radioresistance limits the effectiveness of radiotherapy in head and neck squamous cell carcinoma. We previously demonstrated post-radiogenic mitogen-activated protein kinase (MAPK) pathway activation and vascular endothelial growth factor (VEGF) release resulting in reduced tumor cell response. Here, we examined the association of this mechanism with the induction of reactive oxygen species (ROS) under irradiation (IR). Methods Intracellular ROS after IR were measured. We modeled radiation-induced ROS by exposure of two SCC lines to H2O2 and evaluated the impact of irradiation and ROS on ERK phosphorylation by Western blot, immunohistochemistry, and ELISA. Results We found elevated pERK levels after treatment with IR and H2O2, which could be distinctly suppressed by U0126. Immunohistochemistry and ELISA revealed increased intracellular VEGF levels after H2O2 application. Conclusions Our data show that irradiation-induced ROS activate the MAPK pathway and release of VEGF. As VEGF is known to be released after cellular distress resulting in cytoprotection, the described mechanism is potentially of importance for therapy success.

year	journal	country	edition	language
2013-03-11	Journal of Oral Pathology & Medicine

https://doi.org/10.1111/jop.12056