Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death

作者：Martins Isabelle; Raza Syed Qasim; Voisin Laurent; Dakhli Haithem; Allouch Awatef; Law Frederic; Sabino Dora; De Jong Dorine; Thoreau Maxime; Mintet Elodie; Dugue Delphine; Piacentini Mauro; Gougeon Marie Lise; Jaulin Fanny; Bertrand Pascale; Brenner Catherine; Ojcius David M; Kroemer Guido; Modjtahedi Nazanine; Deutsch Eric; Perfettini Jean Luc^*

来源：Cell Death & Disease, 2018, 9(7): 716.

DOI：10.1038/s41419-018-0747-y

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.

• 出版日期2018-6-18