Therapy response testing of breast cancer in a 3D high-throughput perfused microfluidic platform
Autor: | Junmei Cairns, Richard M. Weinshilboum, Paul Vulto, Jia Yu, Jos Joore, Bart Kramer, Chee Ping Ng, Liewei Wang, Thomas Hankemeier, Sebastiaan Johannes Trietsch, Henriëtte L. Lanz, Anthony D. Saleh |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Cancer Research Pathology Microfluidics Cell Culture Techniques Triple Negative Breast Neoplasms Piperazines chemistry.chemical_compound 3D cell culture 0302 clinical medicine Organ-on-a-chip Outcome Assessment Health Care Triple-negative breast cancer BRCA1 Protein Prognosis lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health Extracellular Matrix Drug Combinations Oncology Technical Advance 030220 oncology & carcinogenesis Female Proteoglycans Collagen medicine.drug medicine.medical_specialty Paclitaxel Cell Survival Antineoplastic Agents lcsh:RC254-282 Olaparib 03 medical and health sciences Breast cancer Cell Line Tumor Genetics medicine Humans Cisplatin business.industry P53 and BRCA1 medicine.disease Personalized medicine 030104 developmental biology chemistry Cell culture Mutation Cancer research Phthalazines Laminin Tumor Suppressor Protein p53 business Triple negative |
Zdroj: | BMC Cancer, 17, 709 BMC Cancer, Vol 17, Iss 1, Pp 1-11 (2017) BMC Cancer |
Popis: | Background Breast cancer is the most common invasive cancer among women. Currently, there are only a few models used for therapy selection, and they are often poor predictors of therapeutic response or take months to set up and assay. In this report, we introduce a microfluidic OrganoPlate® platform for extracellular matrix (ECM) embedded tumor culture under perfusion as an initial study designed to investigate the feasibility of adapting this technology for therapy selection. Methods The triple negative breast cancer cell lines MDA-MB-453, MDA-MB-231 and HCC1937 were selected based on their different BRCA1 and P53 status, and were seeded in the platform. We evaluate seeding densities, ECM composition (Matrigel®, BME2rgf, collagen I) and biomechanical (perfusion vs static) conditions. We then exposed the cells to a series of anti-cancer drugs (paclitaxel, olaparib, cisplatin) and compared their responses to those in 2D cultures. Finally, we generated cisplatin dose responses in 3D cultures of breast cancer cells derived from 2 PDX models. Results The microfluidic platform allows the simultaneous culture of 96 perfused micro tissues, using limited amounts of material, enabling drug screening of patient-derived material. 3D cell culture viability is improved by constant perfusion of the medium. Furthermore, the drug response of these triple negative breast cancer cells was attenuated by culture in 3D and differed from that observed in 2D substrates. Conclusions We have investigated the use of a high-throughput organ-on-a-chip platform to select therapies. Our results have raised the possibility to use this technology in personalized medicine to support selection of appropriate drugs and to predict response to therapy in a real time fashion. Electronic supplementary material The online version of this article (10.1186/s12885-017-3709-3) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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