Irreversible electroporation inhibits pro-cancer inflammatory signaling in triple negative breast cancer cells.
Low-level electric fields have been demonstrated to induce spatial re-distribution of cell membrane receptors when applied for minutes or hours. However, there is limited literature on the influence on cell signaling with short transient high-amplitude pulses typically used in irreversible electroporation (IRE) for cancer treatment. Moreover, literature on signaling pertaining to immune cell trafficking after IRE is conflicting. We hypothesized that pulse parameters (field strength and exposure time) influence cell signaling and subsequently impact immune-cell trafficking. This hypothesis was tested in-vitro on triple negative breast cancer cells treated with IRE, where the effects of pulse parameters on key cell signaling factors were investigated. Importantly, real time PCR mRNA measurements and ELISA protein analyses revealed that thymic stromal lymphopoietin (TSLP) signaling was down regulated by electric field strengths above a critical threshold, irrespective of exposure times spanning those typically used clinically. Comparison with other treatments (thermal shock, chemical poration, kinase inhibitors) revealed that IRE has a unique effect on TSLP. Because TSLP signaling has been demonstrated to drive pro-cancerous immune cell phenotypes in breast and pancreatic cancers, our finding motivates further investigation into the potential use of IRE for induction of an anti-tumor immune response in vivo.
Department of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Ishan
I
Goswami
Department of Biomedical Sciences and Pathology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Sheryl
S
Coutermarsh-Ott
Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Ryan G
RG
Morrison
Department of Biomedical Sciences and Pathology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Irving C
IC
Allen
Department of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA; Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA; Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Rafael V
RV
Davalos
Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA; Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA. Electronic address: sverb@vt.edu.
Scott S
SS
Verbridge
Department of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA; Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA; Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Lissett R
LR
Bickford
D016923:Cell Death; D016207:Cytokines / Q000378:metabolism; D004560:Electricity; D018274:Electroporation; D006801:Humans; D007249:Inflammation / Q000473:pathology; D015398:Signal Transduction; D064726:Triple Negative Breast Neoplasms / Q000473:pathology*; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin
Electroporation; Immunotherapy; Thymic stromal lymphopoietin (TSLP); Triple negative breast cancer
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