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.
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.
Stem Cell Therapies Laboratory, Queensland University of Technology at the Translational Research Institute, Brisbane, Queensland, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia; Australian Prostate Cancer Research Centre, Translational Research Institute, Brisbane, Queensland, Australia.
Karen F
KF
Chambers
Stem Cell Therapies Laboratory, Queensland University of Technology at the Translational Research Institute, Brisbane, Queensland, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia; Australian Prostate Cancer Research Centre, Translational Research Institute, Brisbane, Queensland, Australia.
Eman M O
EM
Mosaad
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia; Australian Prostate Cancer Research Centre, Translational Research Institute, Brisbane, Queensland, Australia.
Pamela J
PJ
Russell
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia; Australian Prostate Cancer Research Centre, Translational Research Institute, Brisbane, Queensland, Australia.
Judith A
JA
Clements
Stem Cell Therapies Laboratory, Queensland University of Technology at the Translational Research Institute, Brisbane, Queensland, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia; Australian Prostate Cancer Research Centre, Translational Research Institute, Brisbane, Queensland, Australia; Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
Michael R
MR
Doran
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D046888:Tissue Array Analysis
D000970:Antineoplastic Agents; D004129:Dimethylpolysiloxanes; C013830:baysilon