Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes.

<h4>Background</h4>Hormone-refractory prostate cancer remains hindered by inevitable progression of resistance to first-line treatment with docetaxel. Recent studies suggest that phenotypic changes associated with cancer may be transferred from cell-to-cell via microvesicles/exosomes. He...

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Autores principales:	Claire Corcoran, Sweta Rani, Keith O'Brien, Amanda O'Neill, Maria Prencipe, Rizwan Sheikh, Glenn Webb, Ray McDermott, William Watson, John Crown, Lorraine O'Driscoll
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a97c7c2322af4f1b9e2ae08a87e51550
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spelling	oai:doaj.org-article:a97c7c2322af4f1b9e2ae08a87e515502021-11-18T08:05:50ZDocetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes.1932-620310.1371/journal.pone.0050999https://doaj.org/article/a97c7c2322af4f1b9e2ae08a87e515502012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23251413/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Hormone-refractory prostate cancer remains hindered by inevitable progression of resistance to first-line treatment with docetaxel. Recent studies suggest that phenotypic changes associated with cancer may be transferred from cell-to-cell via microvesicles/exosomes. Here we aimed to investigate phenotypic changes associated with docetaxel-resistance in order to help determine the complexity of this problem and to assess the relevance of secreted exosomes in prostate cancer.<h4>Methodology/principal findings</h4>Docetaxel-resistant variants of DU145 and 22Rv1 were established and characterised in terms of cross-resistance, morphology, proliferation, motility, invasion, anoikis, colony formation, exosomes secretion their and functional relevance. Preliminary analysis of exosomes from relevant serum specimens was also performed. Acquired docetaxel-resistance conferred cross-resistance to doxorubicin and induced alterations in motility, invasion, proliferation and anchorage-independent growth. Exosomes expelled from DU145 and 22Rv1 docetaxel-resistant variants (DU145RD and 22Rv1RD) conferred docetaxel-resistance to DU145, 22Rv1 and LNCap cells, which may be partly due to exosomal MDR-1/P-gp transfer. Exosomes from prostate cancer patients' sera induced increased cell proliferation and invasion, compared to exosomes from age-matched controls. Furthermore, exosomes from sera of patients undergoing a course of docetaxel treatment compared to matched exosomes from the same patients prior to commencing docetaxel treatment, when applied to both DU145 and 22Rv1 cells, showed a correlation between cellular response to docetaxel and patients' response to treatment with docetaxel.<h4>Conclusions/significance</h4>Our studies indicate the complex and multifaceted nature of docetaxel-resistance in prostate cancer. Furthermore, our in vitro observations and preliminary clinical studies indicate that exosomes may play an important role in prostate cancer, in cell-cell communication, and thus may offer potential as vehicles containing predictive biomarkers and new therapeutic targets.Claire CorcoranSweta RaniKeith O'BrienAmanda O'NeillMaria PrencipeRizwan SheikhGlenn WebbRay McDermottWilliam WatsonJohn CrownLorraine O'DriscollPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e50999 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claire Corcoran Sweta Rani Keith O'Brien Amanda O'Neill Maria Prencipe Rizwan Sheikh Glenn Webb Ray McDermott William Watson John Crown Lorraine O'Driscoll Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes.
description	<h4>Background</h4>Hormone-refractory prostate cancer remains hindered by inevitable progression of resistance to first-line treatment with docetaxel. Recent studies suggest that phenotypic changes associated with cancer may be transferred from cell-to-cell via microvesicles/exosomes. Here we aimed to investigate phenotypic changes associated with docetaxel-resistance in order to help determine the complexity of this problem and to assess the relevance of secreted exosomes in prostate cancer.<h4>Methodology/principal findings</h4>Docetaxel-resistant variants of DU145 and 22Rv1 were established and characterised in terms of cross-resistance, morphology, proliferation, motility, invasion, anoikis, colony formation, exosomes secretion their and functional relevance. Preliminary analysis of exosomes from relevant serum specimens was also performed. Acquired docetaxel-resistance conferred cross-resistance to doxorubicin and induced alterations in motility, invasion, proliferation and anchorage-independent growth. Exosomes expelled from DU145 and 22Rv1 docetaxel-resistant variants (DU145RD and 22Rv1RD) conferred docetaxel-resistance to DU145, 22Rv1 and LNCap cells, which may be partly due to exosomal MDR-1/P-gp transfer. Exosomes from prostate cancer patients' sera induced increased cell proliferation and invasion, compared to exosomes from age-matched controls. Furthermore, exosomes from sera of patients undergoing a course of docetaxel treatment compared to matched exosomes from the same patients prior to commencing docetaxel treatment, when applied to both DU145 and 22Rv1 cells, showed a correlation between cellular response to docetaxel and patients' response to treatment with docetaxel.<h4>Conclusions/significance</h4>Our studies indicate the complex and multifaceted nature of docetaxel-resistance in prostate cancer. Furthermore, our in vitro observations and preliminary clinical studies indicate that exosomes may play an important role in prostate cancer, in cell-cell communication, and thus may offer potential as vehicles containing predictive biomarkers and new therapeutic targets.
format	article
author	Claire Corcoran Sweta Rani Keith O'Brien Amanda O'Neill Maria Prencipe Rizwan Sheikh Glenn Webb Ray McDermott William Watson John Crown Lorraine O'Driscoll
author_facet	Claire Corcoran Sweta Rani Keith O'Brien Amanda O'Neill Maria Prencipe Rizwan Sheikh Glenn Webb Ray McDermott William Watson John Crown Lorraine O'Driscoll
author_sort	Claire Corcoran
title	Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes.
title_short	Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes.
title_full	Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes.
title_fullStr	Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes.
title_full_unstemmed	Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes.
title_sort	docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/a97c7c2322af4f1b9e2ae08a87e51550
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Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes.

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