Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival
| Autor: | Sonia G. Rao, Crystal A. Tonnessen-Murray, Benjamin T. Vinson, Ashkan Shahbandi, Joy O. Olayiwola, Nathan Ungerleider, James G. Jackson, Douglas B. Chrisey, Christopher J. Lord, Lucas B. Murray, Wesley D. Frey |
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| Rok vydání: | 2019 |
| Předmět: |
Senescence
Cell Survival medicine.medical_treatment Cell Population Biology Mice 03 medical and health sciences 0302 clinical medicine Lysosome Tumor Cells Cultured medicine Animals Humans education Cellular Senescence Cell Proliferation 030304 developmental biology 0303 health sciences education.field_of_study Antibiotics Antineoplastic Cell growth Cell Biology Cytokine medicine.anatomical_structure Doxorubicin Apoptosis 030220 oncology & carcinogenesis Cancer cell MCF-7 Cells Cancer research |
| Zdroj: | Journal of Cell Biology. 218:3827-3844 |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.201904051 |
| Popis: | In chemotherapy-treated breast cancer, wild-type p53 preferentially induces senescence over apoptosis, resulting in a persisting cell population constituting residual disease that drives relapse and poor patient survival via the senescence-associated secretory phenotype. Understanding the properties of tumor cells that allow survival after chemotherapy treatment is paramount. Using time-lapse and confocal microscopy to observe interactions of cells in treated tumors, we show here that chemotherapy-induced senescent cells frequently engulf both neighboring senescent or nonsenescent tumor cells at a remarkable frequency. Engulfed cells are processed through the lysosome and broken down, and cells that have engulfed others obtain a survival advantage. Gene expression analysis showed a marked up-regulation of conserved macrophage-like program of engulfment in chemotherapy-induced senescent cell lines and tumors. Our data suggest compelling explanations for how senescent cells persist in dormancy, how they manage the metabolically expensive process of cytokine production that drives relapse in those tumors that respond the worst, and a function for their expanded lysosomal compartment. |
| Databáze: | OpenAIRE |
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