Tumor cell escape from therapy-induced senescence.
Publication/Presentation Date
4-1-2019
Abstract
H460 non-small cell lung, HCT116 colon and 4T1 breast tumor cell lines induced into senescence by exposure to either etoposide or doxorubicin were able to recover proliferative capacity both in mass culture and when enriched for the senescence-like phenotype by flow cytometry (based on β-galactosidase staining and cell size, and a senescence-associated reporter, BTG1-RFP). Recovery was further established using both real-time microscopy and High-Speed Live-Cell Interferometry (HSLCI) and was shown to be accompanied by the attenuation of the Senescence-Associated Secretory Phenotype (SASP). Cells enriched for the senescence-like phenotype were also capable of forming tumors when implanted in both immunodeficient and immunocompetent mice. As chemotherapy-induced senescence has been identified in patient tumors, our results suggest that certain senescence-like phenotypes may not reflect a terminal state of growth arrest, as cells that recover with self-renewal capacity may ultimately contribute to disease recurrence.
Volume
162
First Page
202
Last Page
212
ISSN
1873-2968
Published In/Presented At
Saleh, T., Tyutyunyk-Massey, L., Murray, G. F., Alotaibi, M. R., Kawale, A. S., Elsayed, Z., Henderson, S. C., Yakovlev, V., Elmore, L. W., Toor, A., Harada, H., Reed, J., Landry, J. W., & Gewirtz, D. A. (2019). Tumor cell escape from therapy-induced senescence. Biochemical pharmacology, 162, 202–212. https://doi.org/10.1016/j.bcp.2018.12.013
Disciplines
Medicine and Health Sciences
PubMedID
30576620
Department(s)
Department of Medicine, Hematology-Medical Oncology Division
Document Type
Article