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 of...
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Published in | PloS one Vol. 9; no. 11; p. e111029 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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Public Library of Science
07.11.2014
Public Library of Science (PLoS) |
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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. |
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AbstractList | 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. 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. |
Audience | Academic |
Author | Mosaad, Eman M O Russell, Pamela J Clements, Judith A Doran, Michael R Chambers, Karen F |
AuthorAffiliation | Roswell Park Cancer Institute, United States of America 1 Stem Cell Therapies Laboratory, Queensland University of Technology at the Translational Research Institute, Brisbane, Queensland, Australia 3 Australian Prostate Cancer Research Centre, Translational Research Institute, Brisbane, Queensland, Australia 2 Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia 4 Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia |
AuthorAffiliation_xml | – name: 4 Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia – name: Roswell Park Cancer Institute, United States of America – name: 2 Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia – name: 3 Australian Prostate Cancer Research Centre, Translational Research Institute, Brisbane, Queensland, Australia – name: 1 Stem Cell Therapies Laboratory, Queensland University of Technology at the Translational Research Institute, Brisbane, Queensland, Australia |
Author_xml | – sequence: 1 givenname: Karen F surname: Chambers fullname: Chambers, Karen F organization: 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 – sequence: 2 givenname: Eman M O surname: Mosaad fullname: Mosaad, Eman M O organization: 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 – sequence: 3 givenname: Pamela J surname: Russell fullname: Russell, Pamela J organization: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia; Australian Prostate Cancer Research Centre, Translational Research Institute, Brisbane, Queensland, Australia – sequence: 4 givenname: Judith A surname: Clements fullname: Clements, Judith A organization: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia; Australian Prostate Cancer Research Centre, Translational Research Institute, Brisbane, Queensland, Australia – sequence: 5 givenname: Michael R surname: Doran fullname: Doran, Michael R organization: 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 |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25380249$$D View this record in MEDLINE/PubMed |
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Copyright | COPYRIGHT 2014 Public Library of Science 2014 Chambers et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2014 Chambers et al 2014 Chambers et al |
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Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Conceived and designed the experiments: KFC PJR JAC MRD. Performed the experiments: KFC EMOM. Analyzed the data: KFC. Wrote the paper: KFC. Paper edits: JAC PJR MRD. Competing Interests: The authors have declared that no competing interests exist. |
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SubjectTerms | 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 |
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Title | 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 |
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