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Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo

Senescence is a distinct cellular response induced by DNA-damaging agents and other sublethal stressors and may provide novel benefits in cancer therapy. However, in an ageing model, senescent fibroblasts were found to stimulate the proliferation of cocultured cells. To address whether senescence in...

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Autores principales: Ewald, J A, Desotelle, J A, Almassi, N, Jarrard, D F
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359629/
https://www.ncbi.nlm.nih.gov/pubmed/18349844
http://dx.doi.org/10.1038/sj.bjc.6604288
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author Ewald, J A
Desotelle, J A
Almassi, N
Jarrard, D F
author_facet Ewald, J A
Desotelle, J A
Almassi, N
Jarrard, D F
author_sort Ewald, J A
collection PubMed
description Senescence is a distinct cellular response induced by DNA-damaging agents and other sublethal stressors and may provide novel benefits in cancer therapy. However, in an ageing model, senescent fibroblasts were found to stimulate the proliferation of cocultured cells. To address whether senescence induction in cancer cells using chemotherapy induces similar effects, we used GFP-labelled prostate cancer cell lines and monitored their proliferation in the presence of proliferating or doxorubicin-induced senescent cancer cells in vitro and in vivo. Here, we show that the presence of senescent cancer cells increased the proliferation of cocultured cells in vitro through paracrine signalling factors, but this proliferative effect was significantly less than that seen with senescent fibroblasts. In vivo, senescent cancer cells failed to increase the establishment, growth or proliferation of LNCaP and DU145 xenografts in nude mice. Senescent cells persisted as long as 5 weeks in tumours. Our results demonstrate that although drug-induced senescent cancer cells stimulate the proliferation of bystander cells in vitro, this does not significantly alter the growth of tumours in vivo. Coupled with clinical observations, these data suggest that the proliferative bystander effects of senescent cancer cells are negligible and support the further development of senescence induction as therapy.
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spelling pubmed-23596292009-09-10 Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo Ewald, J A Desotelle, J A Almassi, N Jarrard, D F Br J Cancer Translational Therapeutics Senescence is a distinct cellular response induced by DNA-damaging agents and other sublethal stressors and may provide novel benefits in cancer therapy. However, in an ageing model, senescent fibroblasts were found to stimulate the proliferation of cocultured cells. To address whether senescence induction in cancer cells using chemotherapy induces similar effects, we used GFP-labelled prostate cancer cell lines and monitored their proliferation in the presence of proliferating or doxorubicin-induced senescent cancer cells in vitro and in vivo. Here, we show that the presence of senescent cancer cells increased the proliferation of cocultured cells in vitro through paracrine signalling factors, but this proliferative effect was significantly less than that seen with senescent fibroblasts. In vivo, senescent cancer cells failed to increase the establishment, growth or proliferation of LNCaP and DU145 xenografts in nude mice. Senescent cells persisted as long as 5 weeks in tumours. Our results demonstrate that although drug-induced senescent cancer cells stimulate the proliferation of bystander cells in vitro, this does not significantly alter the growth of tumours in vivo. Coupled with clinical observations, these data suggest that the proliferative bystander effects of senescent cancer cells are negligible and support the further development of senescence induction as therapy. Nature Publishing Group 2008-04-08 2008-03-18 /pmc/articles/PMC2359629/ /pubmed/18349844 http://dx.doi.org/10.1038/sj.bjc.6604288 Text en Copyright © 2008 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Translational Therapeutics
Ewald, J A
Desotelle, J A
Almassi, N
Jarrard, D F
Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo
title Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo
title_full Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo
title_fullStr Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo
title_full_unstemmed Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo
title_short Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo
title_sort drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359629/
https://www.ncbi.nlm.nih.gov/pubmed/18349844
http://dx.doi.org/10.1038/sj.bjc.6604288
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