Epidermal growth factor potentiates EGFR(Y992/1173)-mediated therapeutic response of triple negative breast cancer cells to cold atmospheric plasma-activated medium
Peiyu Wang,
Renwu Zhou,
Rusen Zhou,
Shuo Feng,
Liqian Zhao,
Wenshao Li,
Jinyong Lin,
Aleksandra Rajapakse,
Chia-Hwa Lee,
Frank B. Furnari,
Antony W. Burgess,
Jennifer H. Gunter,
Gang Liu,
Kostya (Ken) Ostrikov,
Derek J. Richard,
Fiona Simpson,
Xiaofeng Dai,
Erik W. Thompson
Affiliations
Peiyu Wang
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China; Centre for Genomics and Personalised Health, School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Translational Research Institute, Woolloongabba, Queensland 4102, Australia; State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, PR China
Renwu Zhou
State Key Laboratory of Electrical Insulation and Power Equipment, Centre for Plasma Biomedicine, School of Electrical Engineering, Xi'an Jiaotong University, Xi'an 710049, PR China
Rusen Zhou
School of Chemistry and Physics, Queensland University of Technology, Brisbane, Queensland 4000, Australia
Shuo Feng
Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China
Liqian Zhao
Department of Neurosurgery, Institute of Brain Disease, Nanfang Hospital of Southern Medical University, Guangzhou 510515, PR China
Wenshao Li
School of Chemistry and Physics, Queensland University of Technology, Brisbane, Queensland 4000, Australia
Jinyong Lin
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, PR China
Aleksandra Rajapakse
Centre for Genomics and Personalised Health, School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Translational Research Institute, Woolloongabba, Queensland 4102, Australia
Chia-Hwa Lee
Centre for Genomics and Personalised Health, School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Translational Research Institute, Woolloongabba, Queensland 4102, Australia
Frank B. Furnari
Department of Medicine, University of California San Diego, California 92093, USA
Antony W. Burgess
Walter and Elisa Hall Institute, Melbourne, Victoria 3052, Australia
Jennifer H. Gunter
Centre for Genomics and Personalised Health, School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Translational Research Institute, Woolloongabba, Queensland 4102, Australia
Gang Liu
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, PR China
Kostya (Ken) Ostrikov
School of Chemistry and Physics, Queensland University of Technology, Brisbane, Queensland 4000, Australia
Derek J. Richard
Centre for Genomics and Personalised Health, School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Translational Research Institute, Woolloongabba, Queensland 4102, Australia; Cancer and Ageing Research Program, Woolloongabba, Queensland 4102, Australia
Fiona Simpson
Frazer Institute, The University of Queensland, Brisbane, Queensland 4102, Australia
Xiaofeng Dai
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China; Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China; Corresponding author. National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
Erik W. Thompson
Centre for Genomics and Personalised Health, School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Translational Research Institute, Woolloongabba, Queensland 4102, Australia
Cold atmospheric plasma (CAP) holds promise as a cancer-specific treatment that selectively kills various types of malignant cells. We used CAP-activated media (PAM) to utilize a range of the generated short- and long-lived reactive species. Specific antibodies, small molecule inhibitors and CRISPR/Cas9 gene-editing approaches showed an essential role for receptor tyrosine kinases, especially epidermal growth factor (EGF) receptor, in mediating triple negative breast cancer (TNBC) cell responses to PAM. EGF also dramatically enhanced the sensitivity and specificity of PAM against TNBC cells. Site-specific phospho-EGFR analysis, signal transduction inhibitors and reconstitution of EGFR-depleted cells with EGFR-mutants confirmed the role of phospho-tyrosines 992/1173 and phospholipase C gamma signaling in up-regulating levels of reactive oxygen species above the apoptotic threshold. EGF-triggered EGFR activation enhanced the sensitivity and selectivity of PAM effects on TNBC cells. The proposed approach based on the synergy of CAP and EGFR-targeted therapy may provide new opportunities to improve the clinical management of TNBC.
