Document Type
Article
Publication Date
2019
Publication Title
Cancers
Volume
11
Pages
2034 (1-18)
DOI
10.3390/cancers11122034
Abstract
Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of immunogenic cell death (ICD) rely on endoplasmic reticulum (ER) stress for the trafficking of danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric fields (nsPEF), an emerging new modality for tumor ablation, cause the activation of the ER-resident stress sensor PERK in both CT-26 colon carcinoma and EL-4 lymphoma cells. PERK activation correlates with sustained CRT exposure on the cell plasma membrane and apoptosis induction in both nsPEF-treated cell lines. Our results show that, in CT-26 cells, the activity of caspase-3/7 was increased fourteen-fold as compared with four-fold in EL-4 cells. Moreover, while nsPEF treatments induced the release of the ICD hallmark HMGB1 in both cell lines, extracellular ATP was detected only in CT-26. Finally, in vaccination assays, CT-26 cells treated with nsPEF or doxorubicin equally impaired the growth of tumors at challenge sites eliciting a protective anticancer immune response in 78% and 80% of the animals, respectively. As compared to CT-26, both nsPEF- and mitoxantrone-treated EL-4 cells had a less pronounced effect and protected 50% and 20% of the animals, respectively. These results support our conclusion that nsPEF induce ER stress, accompanied by bona fide ICD.
Original Publication Citation
Rossi, A., Pakhomova, O. N., Mollica, P. A., Casciola, M., Mangalanathan, U., G Pakhomov, A., & Muratori, C. (2019). Nanosecond pulsed electric fields induce endoplasmic reticulum stress accompanied by immunogenic cell death in murine models of lymphoma and colorectal cancer. Cancers, 11, 1-18, Article 2034. https://doi.org/10.3390/cancers11122034
Repository Citation
Rossi, Alessandra; Pakhomova, Olga N.; Mollica, Peter A.; Casciola, Maura; Mangalanathan, Uma; Pakhomov, Andrei G.; and Muratori, Claudia, "Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied by Immunogenic Cell Death in Murine Models of Lymphoma and Colorectal Cancer" (2019). Bioelectrics Publications. 280.
https://digitalcommons.odu.edu/bioelectrics_pubs/280
ORCID
0000-0003-4950-4130, (Pakhomova), 0000-0002-0621-2819 (Mollica), 0000-0003-3816-3860 (Pakhomov), 0000-0002-3359-164X (Muratori)
Comments
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).