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High expression of TROP2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells
Progression of castration-resistant tumors is frequent in prostate cancer. Current systemic treatments for castration-resistant prostate cancer only produce modest increases in survival time and self-renewing Tumor-Initiating Cells (TICs) are suspected to play an important role in resistance to thes...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190113/ https://www.ncbi.nlm.nih.gov/pubmed/27283984 http://dx.doi.org/10.18632/oncotarget.9876 |
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author | Xie, Jinhan Mølck, Christina Paquet-Fifield, Sophie Butler, Lisa Sloan, Erica Ventura, Sabatino Hollande, Frédéric |
author_facet | Xie, Jinhan Mølck, Christina Paquet-Fifield, Sophie Butler, Lisa Sloan, Erica Ventura, Sabatino Hollande, Frédéric |
author_sort | Xie, Jinhan |
collection | PubMed |
description | Progression of castration-resistant tumors is frequent in prostate cancer. Current systemic treatments for castration-resistant prostate cancer only produce modest increases in survival time and self-renewing Tumor-Initiating Cells (TICs) are suspected to play an important role in resistance to these treatments. However it remains unclear whether the same TICs display both chemo-resistance and self-renewing abilities throughout progression from early stage lesions to late, castration resistant tumors. Here, we found that treatment of mice bearing LNCaP-derived xenograft tumors with cytotoxic (docetaxel) and anti-androgen (flutamide) compounds enriched for cells that express TROP2, a putative TIC marker. Consistent with a tumor-initiating role, TROP2(high) cells from androgen-sensitive prostate cancer cell lines displayed an enhanced ability to re-grow in culture following treatment with taxane-based chemotherapy with or without androgen blockade. TROP2 down-regulation in these cells reduced their ability to recur after treatment with docetaxel, in the presence or absence of flutamide. Accordingly, in silico analysis of published clinical data revealed that prostate cancer patients with poor prognosis exhibit significantly elevated TROP2 expression level compared to low-risk patients, particularly in the case of patients diagnosed with early stage tumors. In contrast, in androgen-independent prostate cancer cell lines, TROP2(high) cells did not exhibit a differential treatment response but were characterized by their high self-renewal ability. Based on these findings we propose that high TROP2 expression identifies distinct cell sub-populations in androgen-sensitive and androgen-independent prostate tumors and that it may be a predictive biomarker for prostate cancer treatment response in androgen-sensitive tumors. |
format | Online Article Text |
id | pubmed-5190113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-51901132017-01-05 High expression of TROP2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells Xie, Jinhan Mølck, Christina Paquet-Fifield, Sophie Butler, Lisa Sloan, Erica Ventura, Sabatino Hollande, Frédéric Oncotarget Research Paper Progression of castration-resistant tumors is frequent in prostate cancer. Current systemic treatments for castration-resistant prostate cancer only produce modest increases in survival time and self-renewing Tumor-Initiating Cells (TICs) are suspected to play an important role in resistance to these treatments. However it remains unclear whether the same TICs display both chemo-resistance and self-renewing abilities throughout progression from early stage lesions to late, castration resistant tumors. Here, we found that treatment of mice bearing LNCaP-derived xenograft tumors with cytotoxic (docetaxel) and anti-androgen (flutamide) compounds enriched for cells that express TROP2, a putative TIC marker. Consistent with a tumor-initiating role, TROP2(high) cells from androgen-sensitive prostate cancer cell lines displayed an enhanced ability to re-grow in culture following treatment with taxane-based chemotherapy with or without androgen blockade. TROP2 down-regulation in these cells reduced their ability to recur after treatment with docetaxel, in the presence or absence of flutamide. Accordingly, in silico analysis of published clinical data revealed that prostate cancer patients with poor prognosis exhibit significantly elevated TROP2 expression level compared to low-risk patients, particularly in the case of patients diagnosed with early stage tumors. In contrast, in androgen-independent prostate cancer cell lines, TROP2(high) cells did not exhibit a differential treatment response but were characterized by their high self-renewal ability. Based on these findings we propose that high TROP2 expression identifies distinct cell sub-populations in androgen-sensitive and androgen-independent prostate tumors and that it may be a predictive biomarker for prostate cancer treatment response in androgen-sensitive tumors. Impact Journals LLC 2016-06-07 /pmc/articles/PMC5190113/ /pubmed/27283984 http://dx.doi.org/10.18632/oncotarget.9876 Text en Copyright: © 2016 Xie et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Xie, Jinhan Mølck, Christina Paquet-Fifield, Sophie Butler, Lisa Sloan, Erica Ventura, Sabatino Hollande, Frédéric High expression of TROP2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells |
title | High expression of TROP2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells |
title_full | High expression of TROP2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells |
title_fullStr | High expression of TROP2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells |
title_full_unstemmed | High expression of TROP2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells |
title_short | High expression of TROP2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells |
title_sort | high expression of trop2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190113/ https://www.ncbi.nlm.nih.gov/pubmed/27283984 http://dx.doi.org/10.18632/oncotarget.9876 |
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