Senescence, Necrosis, and Apoptosis Govern Circulating Cell-free DNA Release Kinetics
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720308111 |
| _version_ | 1818498607481880576 |
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| author | Ariana Rostami Meghan Lambie Caberry W. Yu Vuk Stambolic John N. Waldron Scott V. Bratman |
| author_facet | Ariana Rostami Meghan Lambie Caberry W. Yu Vuk Stambolic John N. Waldron Scott V. Bratman |
| author_sort | Ariana Rostami |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T20:17:54Z |
| format | Article |
| id | doaj.art-df1d58749d0d4dd696896af974a068ae |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T20:17:54Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-df1d58749d0d4dd696896af974a068ae2022-12-22T01:35:09ZengElsevierCell Reports2211-12472020-06-013113107830Senescence, Necrosis, and Apoptosis Govern Circulating Cell-free DNA Release KineticsAriana Rostami0Meghan Lambie1Caberry W. Yu2Vuk Stambolic3John N. Waldron4Scott V. Bratman5Princess Margaret Cancer Center, University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, CanadaPrincess Margaret Cancer Center, University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, CanadaPrincess Margaret Cancer Center, University Health Network, 101 College Street, Toronto, ON M5G 1L7, CanadaPrincess Margaret Cancer Center, University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, CanadaPrincess Margaret Cancer Center, University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada; Department of Radiation Oncology, University of Toronto, 149 College Street, Toronto, ON M5T 1P5, CanadaPrincess Margaret Cancer Center, University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada; Department of Radiation Oncology, University of Toronto, 149 College Street, Toronto, ON M5T 1P5, Canada; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720308111circulating cell-free DNAliquid biopsytreatment monitoringkineticssenescencenecrosis |
| spellingShingle | Ariana Rostami Meghan Lambie Caberry W. Yu Vuk Stambolic John N. Waldron Scott V. Bratman Senescence, Necrosis, and Apoptosis Govern Circulating Cell-free DNA Release Kinetics Cell Reports circulating cell-free DNA liquid biopsy treatment monitoring kinetics senescence necrosis |
| title | Senescence, Necrosis, and Apoptosis Govern Circulating Cell-free DNA Release Kinetics |
| title_full | Senescence, Necrosis, and Apoptosis Govern Circulating Cell-free DNA Release Kinetics |
| title_fullStr | Senescence, Necrosis, and Apoptosis Govern Circulating Cell-free DNA Release Kinetics |
| title_full_unstemmed | Senescence, Necrosis, and Apoptosis Govern Circulating Cell-free DNA Release Kinetics |
| title_short | Senescence, Necrosis, and Apoptosis Govern Circulating Cell-free DNA Release Kinetics |
| title_sort | senescence necrosis and apoptosis govern circulating cell free dna release kinetics |
| topic | circulating cell-free DNA liquid biopsy treatment monitoring kinetics senescence necrosis |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720308111 |
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