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

• Published in: PloS one Vol. 9; no. 11; p. e111029
• Main Authors: Chambers, Karen F, Mosaad, Eman M O, Russell, Pamela J, Clements, Judith A, Doran, Michael R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.11.2014; Public Library of Science (PLoS)
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biology; Biology and Life Sciences; Cancer; Cancer cells; Cell adhesion & migration; Cell Aggregation - drug effects; Cell culture; Cell Culture Techniques - methods; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemotherapy; Dimethylpolysiloxanes - chemistry; Drug development; Drug Resistance, Neoplasm - drug effects; Drug testing; Engineering and Technology; Extracellular matrix; Growth kinetics; Humans; In vivo methods and tests; Kinetics; Laboratories; Male; Medical research; Medical screening; Medicine and Health Sciences; Monolayers; Monomolecular films; Morphogenesis; Polarity; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Research and Analysis Methods; Stem cells; Tissue Array Analysis; Tissues; Tumors; Queensland Australia; Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0111029

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.