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Early Human Prostate Adenocarcinomas Harbor Androgen-Independent Cancer Cells

Although blockade of androgen receptor (AR) signaling represents the main treatment for advanced prostate cancer (PrCa), many patients progress to a lethal phenotype of “Castration-Resistant” prostate cancer (CR-PrCa). With the hypothesis that early PrCa may harbor a population of androgen-unrespons...

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Autores principales: Fiñones, Rita R., Yeargin, Jo, Lee, Melissa, Kaur, Aman Preet, Cheng, Clari, Sun, Paulina, Wu, Christopher, Nguyen, Catherine, Wang-Rodriguez, Jessica, Meyer, April N., Baird, Stephen M., Donoghue, Daniel J., Haas, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783414/
https://www.ncbi.nlm.nih.gov/pubmed/24086346
http://dx.doi.org/10.1371/journal.pone.0074438
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author Fiñones, Rita R.
Yeargin, Jo
Lee, Melissa
Kaur, Aman Preet
Cheng, Clari
Sun, Paulina
Wu, Christopher
Nguyen, Catherine
Wang-Rodriguez, Jessica
Meyer, April N.
Baird, Stephen M.
Donoghue, Daniel J.
Haas, Martin
author_facet Fiñones, Rita R.
Yeargin, Jo
Lee, Melissa
Kaur, Aman Preet
Cheng, Clari
Sun, Paulina
Wu, Christopher
Nguyen, Catherine
Wang-Rodriguez, Jessica
Meyer, April N.
Baird, Stephen M.
Donoghue, Daniel J.
Haas, Martin
author_sort Fiñones, Rita R.
collection PubMed
description Although blockade of androgen receptor (AR) signaling represents the main treatment for advanced prostate cancer (PrCa), many patients progress to a lethal phenotype of “Castration-Resistant” prostate cancer (CR-PrCa). With the hypothesis that early PrCa may harbor a population of androgen-unresponsive cancer cells as precursors to CR-recurrent disease, we undertook the propagation of androgen-independent cells from PrCa-prostatectomy samples of early, localized (Stage-I) cases. A collection of 120 surgical specimens from prostatectomy cases was established, among which 54 were adenocarcinomas. Hormone-free cell culture conditions were developed allowing routine propagation of cells expressing prostate basal cell markers and stem/progenitor cell markers, and which proliferated as spheres/spheroids in suspension cultures. Colonies of androgen-independent epithelial cells grew out from 30/43 (70%) of the adenocarcinoma cases studied in detail. Fluorescence microscopy and flow cytometry showed that CR-PrCa cells were positive for CD44, CD133, CK5/14, c-kit, integrin α2β1, SSEA4, E-Cadherin and Aldehyde Dehydrogenase (ALDH). All 30 CR-PrCa cell cultures were also TERT-positive, but negative for TMPRSS2-ERG. Additionally, a subset of 22 of these CR-PrCa cell cultures was examined by orthotopic xenografting in intact and castrated SCID mice, generating histologically typical locally-invasive human PrCa or undifferentiated cancers, respectively, in 6–8 weeks. Cultured PrCa cells and orthotopically-induced in vivo cancers lacked PSA expression. We report here the propagation of Cancer Initiating Cells (CIC) directly from Stage I human PrCa tissue without selection or genetic manipulation. The propagation of stem/progenitor-like CR-PrCa cells derived from early human prostate carcinomas suggests the existence of a subpopulation of cells resistant to androgen-deprivation therapy and which may drive the subsequent emergence of disseminated CR-PrCa.
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spelling pubmed-37834142013-10-01 Early Human Prostate Adenocarcinomas Harbor Androgen-Independent Cancer Cells Fiñones, Rita R. Yeargin, Jo Lee, Melissa Kaur, Aman Preet Cheng, Clari Sun, Paulina Wu, Christopher Nguyen, Catherine Wang-Rodriguez, Jessica Meyer, April N. Baird, Stephen M. Donoghue, Daniel J. Haas, Martin PLoS One Research Article Although blockade of androgen receptor (AR) signaling represents the main treatment for advanced prostate cancer (PrCa), many patients progress to a lethal phenotype of “Castration-Resistant” prostate cancer (CR-PrCa). With the hypothesis that early PrCa may harbor a population of androgen-unresponsive cancer cells as precursors to CR-recurrent disease, we undertook the propagation of androgen-independent cells from PrCa-prostatectomy samples of early, localized (Stage-I) cases. A collection of 120 surgical specimens from prostatectomy cases was established, among which 54 were adenocarcinomas. Hormone-free cell culture conditions were developed allowing routine propagation of cells expressing prostate basal cell markers and stem/progenitor cell markers, and which proliferated as spheres/spheroids in suspension cultures. Colonies of androgen-independent epithelial cells grew out from 30/43 (70%) of the adenocarcinoma cases studied in detail. Fluorescence microscopy and flow cytometry showed that CR-PrCa cells were positive for CD44, CD133, CK5/14, c-kit, integrin α2β1, SSEA4, E-Cadherin and Aldehyde Dehydrogenase (ALDH). All 30 CR-PrCa cell cultures were also TERT-positive, but negative for TMPRSS2-ERG. Additionally, a subset of 22 of these CR-PrCa cell cultures was examined by orthotopic xenografting in intact and castrated SCID mice, generating histologically typical locally-invasive human PrCa or undifferentiated cancers, respectively, in 6–8 weeks. Cultured PrCa cells and orthotopically-induced in vivo cancers lacked PSA expression. We report here the propagation of Cancer Initiating Cells (CIC) directly from Stage I human PrCa tissue without selection or genetic manipulation. The propagation of stem/progenitor-like CR-PrCa cells derived from early human prostate carcinomas suggests the existence of a subpopulation of cells resistant to androgen-deprivation therapy and which may drive the subsequent emergence of disseminated CR-PrCa. Public Library of Science 2013-09-25 /pmc/articles/PMC3783414/ /pubmed/24086346 http://dx.doi.org/10.1371/journal.pone.0074438 Text en © 2013 Fiñones et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Fiñones, Rita R.
Yeargin, Jo
Lee, Melissa
Kaur, Aman Preet
Cheng, Clari
Sun, Paulina
Wu, Christopher
Nguyen, Catherine
Wang-Rodriguez, Jessica
Meyer, April N.
Baird, Stephen M.
Donoghue, Daniel J.
Haas, Martin
Early Human Prostate Adenocarcinomas Harbor Androgen-Independent Cancer Cells
title Early Human Prostate Adenocarcinomas Harbor Androgen-Independent Cancer Cells
title_full Early Human Prostate Adenocarcinomas Harbor Androgen-Independent Cancer Cells
title_fullStr Early Human Prostate Adenocarcinomas Harbor Androgen-Independent Cancer Cells
title_full_unstemmed Early Human Prostate Adenocarcinomas Harbor Androgen-Independent Cancer Cells
title_short Early Human Prostate Adenocarcinomas Harbor Androgen-Independent Cancer Cells
title_sort early human prostate adenocarcinomas harbor androgen-independent cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783414/
https://www.ncbi.nlm.nih.gov/pubmed/24086346
http://dx.doi.org/10.1371/journal.pone.0074438
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