Tumor cell escape from therapy-induced senescence.

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.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Saleh T,Tyutyunyk-Massey L,Murray GF,Alotaibi MR,Kawale AS,Elsayed Z,Henderson SC,Yakovlev V,Elmore LW,Toor A,Harada H,Reed J,Landry JW,Gewirtz DA

doi

10.1016/j.bcp.2018.12.013

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

202-212

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(18)30512-4

journal_volume

162

pub_type

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