Type

Journal Article

Authors

John Crown
William Watson
Ray McDermott
Glenn Webb
Rizwan Sheikh
Maria Prencipe
Amanda O'Neill
Lorraine O'Driscoll
Keith O'Brien
Sweta Rani
and 1 others

Subjects

Medicine & Nursing

Topics
docetaxel cell communication cell proliferation taxoids therapeutic use therapeutic targets drug effects humans prostatic neoplasms cancer patients p gp cellular response cell movement genetics drug discovery profiling targeting drug therapy cross resistance exosomes cancer treatment male cancer drug resistance neoplasm pathology prostate cancer physiology pharmacology cell line tumor phenotype

Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes. (2012)

Abstract Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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.
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Full list of authors on original publication

John Crown, William Watson, Ray McDermott, Glenn Webb, Rizwan Sheikh, Maria Prencipe, Amanda O'Neill, Lorraine O'Driscoll, Keith O'Brien, Sweta Rani and 1 others

Experts in our system

1
John Crown
Dublin City University
Total Publications: 104
 
2
William R Watson
Trinity College Dublin
 
3
Ray McDermott
TU Dublin (Tallaght Campus)
Total Publications: 20
 
4
Maria Prencipe
University College Dublin
Total Publications: 19
 
5
Amanda J O'Neill
University College Dublin
Total Publications: 46
 
6
Lorraine O'Driscoll
Trinity College Dublin
Total Publications: 164
 
7
Sweta Rani
Trinity College Dublin