Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death.
ORCiD
David M. Ojcius: 0000-0003-1461-4495
Department
Biomedical Sciences
Document Type
Article
Publication Title
Cell Death and Disease
ISSN
2041-4889
Volume
9
Issue
7
DOI
10.1038/s41419-018-0747-y
First Page
1
Last Page
18
Publication Date
6-18-2018
Abstract
Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells. After ionizing radiation, oxaliplatin, or cisplatin treatment, fractions of treated cancer cell populations were eliminated through cell-autonomous death mechanisms, while other fractions of the treated cancer cells engulfed and killed neighboring cells through non-cell-autonomous processes, including cellular cannibalism. Under conditions of treatment with paclitaxel, non-cell-autonomous and cell-autonomous death were both detected in the treated cell population, while untreated neighboring cells exhibited features of apoptotic demise. The transcriptional activity of p53 tumor-suppressor protein contributed to the execution of cell-autonomous death, yet failed to affect the non-cell-autonomous death by cannibalism for the majority of tested anticancer agents, indicating that the induction of non-cell-autonomous death can occur under conditions in which cell-autonomous death was impaired. Altogether, these results reveal that chemotherapy and radiotherapy can induce both non-cell-autonomous and cell-autonomous death of cancer cells, highlighting the heterogeneity of cell death responses to anticancer treatments and the unsuspected potential contribution of non-cell-autonomous death to the global effects of anticancer treatment.
Recommended Citation
Martins, I.,
Raza, S. Q.,
Voisin, L.,
Dakhli, H.,
Allouch, A.,
Law, F.,
Sabino, D.,
De Jong, D.,
Thoreau, M.,
Mintet, E.,
Dugué, D.,
Piacentini, M.,
Gougeon, M.,
Jaulin, F.,
Bertrand, P.,
Brenner, C.,
Ojcius, D. M.,
Kroemer, G.,
Modjtahedi, N.,
Deutsch, E.,
&
Perfettini, J.
(2018).
Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death..
Cell Death and Disease, 9(7), 1–18.
DOI: 10.1038/s41419-018-0747-y
https://scholarlycommons.pacific.edu/dugoni-facarticles/435
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
