Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy
Autor: | John W.M. Martens, Sylvia E. Le Dévédec, Gerhard A. Burger, Leo S. Price, Liesanne Wolters, Marcel Smid, Peter Stoilov, Bram Herpers, Kuan Yan, Bob van de Water, Esmee Koedoot |
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Přispěvatelé: | Medical Oncology |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Science
medicine.medical_treatment Cell Culture Techniques Breast Neoplasms Biology Article Targeted therapy Transcriptome Extracellular matrix 03 medical and health sciences 0302 clinical medicine Drug Delivery Systems Breast cancer SDG 3 - Good Health and Well-being Cyclin-dependent kinase Cell Line Tumor medicine Cancer genomics Humans 030304 developmental biology Cancer 0303 health sciences Multidisciplinary Kinase Cell cycle Cellular Reprogramming 3. Good health Cell culture 030220 oncology & carcinogenesis Cancer research biology.protein Medicine Female Drug Screening Assays Antitumor Reprogramming Cell signalling |
Zdroj: | Scientific Reports, 11, 7529 Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) Scientific Reports, 11(1):7259. Nature Publishing Group |
ISSN: | 2045-2322 |
Popis: | Screening for effective candidate drugs for breast cancer has shifted from two-dimensional (2D) to three-dimensional (3D) cultures. Here we systematically compared the transcriptomes of these different culture conditions by RNAseq of 14 BC cell lines cultured in both 2D and 3D conditions. All 3D BC cell cultures demonstrated increased mitochondrial metabolism and downregulated cell cycle programs. Luminal BC cells in 3D demonstrated overall limited reprogramming. 3D basal B BC cells showed increased expression of extracellular matrix (ECM) interaction genes, which coincides with an invasive phenotype not observed in other BC cells. Genes downregulated in 3D were associated with metastatic disease progression in BC patients, including cyclin dependent kinases and aurora kinases. Furthermore, the overall correlation of the cell line transcriptome to the BC patient transcriptome was increased in 3D cultures for all TNBC cell lines. To define the most optimal culture conditions to study the oncogenic pathway of interest, an open source bioinformatics strategy was established. |
Databáze: | OpenAIRE |
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