Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Xie, Jinhan, Mølck, Christina, Paquet-Fifield, Sophie, Butler, Lisa, Sloan, Erica, Ventura, Sabatino, Hollande, Frédéric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
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
_version_ 1782487355164196864
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
work_keys_str_mv AT xiejinhan highexpressionoftrop2characterizesdifferentcellsubpopulationsinandrogensensitiveandandrogenindependentprostatecancercells
AT mølckchristina highexpressionoftrop2characterizesdifferentcellsubpopulationsinandrogensensitiveandandrogenindependentprostatecancercells
AT paquetfifieldsophie highexpressionoftrop2characterizesdifferentcellsubpopulationsinandrogensensitiveandandrogenindependentprostatecancercells
AT butlerlisa highexpressionoftrop2characterizesdifferentcellsubpopulationsinandrogensensitiveandandrogenindependentprostatecancercells
AT highexpressionoftrop2characterizesdifferentcellsubpopulationsinandrogensensitiveandandrogenindependentprostatecancercells
AT sloanerica highexpressionoftrop2characterizesdifferentcellsubpopulationsinandrogensensitiveandandrogenindependentprostatecancercells
AT venturasabatino highexpressionoftrop2characterizesdifferentcellsubpopulationsinandrogensensitiveandandrogenindependentprostatecancercells
AT hollandefrederic highexpressionoftrop2characterizesdifferentcellsubpopulationsinandrogensensitiveandandrogenindependentprostatecancercells