3D cultures of prostate cancer cells cultured in a novel high-throughput culture platform are more resistant to chemotherapeutics compared to cells cultured in monolayer

Huss, Wendy J., Chambers, Karen F., Mosaad, Eman M.O., Russell, Pamela J., Clements, Judith A., & Doran, Michael R. (2014) 3D cultures of prostate cancer cells cultured in a novel high-throughput culture platform are more resistant to chemotherapeutics compared to cells cultured in monolayer. PLoS ONE, 9(11), e111029.

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Abstract

Despite monolayer cultures being widely used for cancer drug development and testing, 2D cultures tend to be hypersensitive to chemotherapy and are relatively poor predictors of whether a drug will provide clinical benefit. Whilst generally more complicated, three dimensional (3D) culture systems often better recapitulate true cancer architecture and provide a more accurate drug response. As a step towards making 3D cancer cultures more accessible, we have developed a microwell platform and surface modification protocol to enable high throughput manufacture of 3D cancer aggregates. Herein we use this novel system to characterize prostate cancer cell microaggregates, including growth kinetics and drug sensitivity. Our results indicate that prostate cancer cells are viable in this system, however some non-cancerous prostate cell lines are not. This system allows us to consistently control for the presence or absence of an apoptotic core in the 3D cancer microaggregates. Similar to tumor tissues, the 3D microaggregates display poor polarity. Critically the response of 3D microaggregates to the chemotherapeutic drug, docetaxel, is more consistent with in vivo results than the equivalent 2D controls. Cumulatively, our results demonstrate that these prostate cancer microaggregates better recapitulate the morphology of prostate tumors compared to 2D and can be used for high-throughput drug testing.

Impact and interest:

21 citations in Scopus
20 citations in Web of Science®
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ID Code: 84360
Item Type: Journal Article
Refereed: Yes
Keywords: Prostate cancer, Cell polarity, Cell staining, Cell metabolism, Apoptosis
DOI: 10.1371/journal.pone.0111029
ISSN: 1932-6203
Divisions: Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2014 Chambers et al.
Copyright Statement: 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 credited.
Deposited On: 21 May 2015 00:44
Last Modified: 14 Sep 2016 02:49

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