Multinucleated polyploidy drives resistance to Docetaxel chemotherapy in prostate cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-04

AUTHORS

Karuna Mittal, Shashi Donthamsetty, Ramneet Kaur, Chunhua Yang, Meenakshi V Gupta, Michelle D Reid, Da Hoon Choi, Padmashree C G Rida, Ritu Aneja

ABSTRACT

BACKGROUND: Docetaxel is the only FDA-approved first-line treatment for castration-resistant prostate cancer (CRPC) patients. Docetaxel treatment inevitably leads to tumour recurrence after an initial therapeutic response with generation of multinucleated polyploid (MP) cells. Here we investigated role of MP cells in clinical relapse of CRPC. METHODS: Prostate cancer (PC-3) cells were treated with docetaxel (5 nM) for 3 days followed by a washout and samples were collected at close intervals over 35 days post drug washout. The tumorigenic potential of the giant MP cells was studied by implanting MP cells subcutaneously as tumour xenografts in nude mice. RESULTS: Docetaxel-induced polyploid cells undergo mitotic slippage and eventually spawn mononucleated cells via asymmetric cell division or neosis. Both MP and cells derived from polyploid cells had increased survival signals, were positive for CD44 and were resistant to docetaxel chemotherapy. Although MP cells were tumorigenic in nude mice, these cells took a significantly longer time to form tumours compared with parent PC-3 cells. CONCLUSIONS: Generation of MP cells upon docetaxel therapy is an adaptive response of apoptosis-reluctant cells. These giant cells ultimately contribute to the generation of mononucleated aneuploid cells via neosis and may have a fundamental role precipitating clinical relapse and chemoresistance in CRPC. More... »

PAGES

1186

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.2017.78

DOI

http://dx.doi.org/10.1038/bjc.2017.78

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084127761

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28334734


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RDF/XML is a standard XML format for linked data.

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