The following study was conducted by Scientists from Princess Margaret Cancer Center, University Health Network, 101 College Street, Toronto, Canada; Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, Canada; Department of Radiation Oncology, University of Toronto, 149 College Street, Toronto, Canada. Study is published in Cell Reports Journal – Cell Press Publishing as detailed below.
Cell Reports Journal – Cell Press Publishing (2020)
Senescence, Necrosis, and Apoptosis Govern Circulating Cell-free DNA Release Kinetics
Highlights
- Treatment type can induce different kinetics of cell-free DNA (cfDNA) release
- Irradiation-induced necrosis is a key contributor of cfDNA release in preclinical models of cancer
- Cellular senescence is a major determinant of cfDNA kinetics and blocks its release
- Selective elimination of senescent cells through apoptosis increases cfDNA release
Summary
The kinetics of circulating cell-free DNA (cfDNA) release may provide a real-time assessment of induced cell death. However, there is a limited understanding of the underlying biological rationale for cfDNA release following distinct treatments and cell death mechanisms. Here, we uncover a complex interplay between apoptosis, necrosis, and senescence in determining cfDNA release kinetics. Utilizing multiple in vitro and in vivo preclinical models, we show how cfDNA release is modulated through a combination of apoptotic and senescent triggers and inhibitors. Interestingly, we identify treatment-induced senescence as a previously unrecognized determinant of cfDNA kinetics that can counteract its release. Necrosis is the predominant cell death mechanism that consistently contributes to cfDNA release in response to ionizing radiation, and, surprisingly, apoptosis plays a comparatively minor role in some tumors. Based on our results, we propose a model to explain cfDNA release from cells over time, with important implications for future studies.
Source:
Cell Reports Journal – Cell Press Publishing
URL: https://www.cell.com/cell-reports/fulltext/S2211-1247(20)30811-1
Citation:
Rostami, A., M. Lambie, et al. (2020). “Senescence, Necrosis, and Apoptosis Govern Circulating Cell-free DNA Release Kinetics.” Cell Reports 31(13).
