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
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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