Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes
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 phen...
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| creator | Corcoran, Claire Rani, Sweta O'Brien, Keith O'Neill, Amanda Prencipe, Maria Sheikh, Rizwan Webb, Glenn McDermott, Ray Watson, William Crown, John O'Driscoll, Lorraine |
| description | 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.
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.
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. |
| doi_str_mv | 10.1371/journal.pone.0050999 |
| format | Article |
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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.
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0050999</identifier><identifier>PMID: 23251413</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Androgens ; Anoikis ; Anthracyclines ; Biomarkers ; Cancer ; Cell cycle ; Cell interactions ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell proliferation ; Cell Proliferation - drug effects ; Cell signaling ; Communication ; Complexity ; Cross-resistance ; Development and progression ; Docetaxel ; Doxorubicin ; Drug Resistance, Neoplasm - physiology ; Exosomes ; Exosomes - drug effects ; Exosomes - genetics ; Humans ; Male ; MDR1 protein ; Medicine ; Morphology ; Motility ; P-Glycoprotein ; Patients ; Pharmaceutical sciences ; Pharmacy ; Phenotype ; Prostate cancer ; Prostatic Neoplasms - drug therapy ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - pathology ; Secretion ; Signal transduction ; Taxoids - pharmacology ; Taxoids - therapeutic use ; Wound healing</subject><ispartof>PloS one, 2012-12, Vol.7 (12), p.e50999-e50999</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Corcoran et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Corcoran et al 2012 Corcoran et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-df7c0d2ba53806f03d10606c954a7d5f8e8524a615312e58f932d8e13625c713</citedby><cites>FETCH-LOGICAL-c758t-df7c0d2ba53806f03d10606c954a7d5f8e8524a615312e58f932d8e13625c713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519481/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519481/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23251413$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kyprianou, Natasha</contributor><creatorcontrib>Corcoran, Claire</creatorcontrib><creatorcontrib>Rani, Sweta</creatorcontrib><creatorcontrib>O'Brien, Keith</creatorcontrib><creatorcontrib>O'Neill, Amanda</creatorcontrib><creatorcontrib>Prencipe, Maria</creatorcontrib><creatorcontrib>Sheikh, Rizwan</creatorcontrib><creatorcontrib>Webb, Glenn</creatorcontrib><creatorcontrib>McDermott, Ray</creatorcontrib><creatorcontrib>Watson, William</creatorcontrib><creatorcontrib>Crown, John</creatorcontrib><creatorcontrib>O'Driscoll, Lorraine</creatorcontrib><title>Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.
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.
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.</description><subject>Analysis</subject><subject>Androgens</subject><subject>Anoikis</subject><subject>Anthracyclines</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cell interactions</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell signaling</subject><subject>Communication</subject><subject>Complexity</subject><subject>Cross-resistance</subject><subject>Development and progression</subject><subject>Docetaxel</subject><subject>Doxorubicin</subject><subject>Drug Resistance, Neoplasm - physiology</subject><subject>Exosomes</subject><subject>Exosomes - 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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.
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.
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23251413</pmid><doi>10.1371/journal.pone.0050999</doi><tpages>e50999</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1339597712 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Analysis Androgens Anoikis Anthracyclines Biomarkers Cancer Cell cycle Cell interactions Cell Line, Tumor Cell Movement - drug effects Cell proliferation Cell Proliferation - drug effects Cell signaling Communication Complexity Cross-resistance Development and progression Docetaxel Doxorubicin Drug Resistance, Neoplasm - physiology Exosomes Exosomes - drug effects Exosomes - genetics Humans Male MDR1 protein Medicine Morphology Motility P-Glycoprotein Patients Pharmaceutical sciences Pharmacy Phenotype Prostate cancer Prostatic Neoplasms - drug therapy Prostatic Neoplasms - genetics Prostatic Neoplasms - pathology Secretion Signal transduction Taxoids - pharmacology Taxoids - therapeutic use Wound healing |
| title | Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T06%3A54%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Docetaxel-resistance%20in%20prostate%20cancer:%20evaluating%20associated%20phenotypic%20changes%20and%20potential%20for%20resistance%20transfer%20via%20exosomes&rft.jtitle=PloS%20one&rft.au=Corcoran,%20Claire&rft.date=2012-12-10&rft.volume=7&rft.issue=12&rft.spage=e50999&rft.epage=e50999&rft.pages=e50999-e50999&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0050999&rft_dat=%3Cgale_plos_%3EA477084030%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1339597712&rft_id=info:pmid/23251413&rft_galeid=A477084030&rft_doaj_id=oai_doaj_org_article_a97c7c2322af4f1b9e2ae08a87e51550&rfr_iscdi=true |