Breast cancer patient‐derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments
Autor: | Joakim Håkansson, Anna Gustafsson, Elena Garre, Anders Ståhlberg, Göran Landberg, Maria Carmen Leiva, Yalda Bogestål, Andreas Svanström |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Physiology Clinical Biochemistry Cell Culture Techniques chemotherapy Extracellular matrix chemistry.chemical_compound 0302 clinical medicine Original Research Articles Tumor Microenvironment Medicine Original Research Article Tissue Scaffolds Gene Expression Regulation Neoplastic Phenotype Paclitaxel 3D in vitro culture 030220 oncology & carcinogenesis Printing Three-Dimensional MCF-7 Cells Neoplastic Stem Cells Female Fluorouracil medicine.drug extracellular matrix Antineoplastic Agents Breast Neoplasms 03 medical and health sciences breast cancer Breast cancer Cancer stem cell Humans Doxorubicin Cell Proliferation Tumor microenvironment Dose-Response Relationship Drug business.industry Cell Biology medicine.disease 030104 developmental biology chemistry Drug Resistance Neoplasm Tumor progression Cancer cell Cancer research decellularized scaffold Drug Screening Assays Antitumor Transcriptome business |
Zdroj: | Journal of Cellular Physiology |
ISSN: | 1097-4652 0021-9541 |
Popis: | Breast cancer is a heterogeneous disease where the tumor microenvironment, including extracellular components, plays a crucial role in tumor progression, potentially modulating treatment response. Different approaches have been used to develop three‐dimensional models able to recapitulate the complexity of the extracellular matrix. Here, we use cell‐free patient‐derived scaffolds (PDSs) generated from breast cancer samples that were recellularized with cancer cell lines as an in vivo‐like culture system for drug testing. We show that PDS cultured MCF7 cancer cells increased their resistance against the front‐line chemotherapy drugs 5‐fluorouracil, doxorubicin and paclitaxel in comparison to traditional two‐dimensional cell cultures. The gene expression of the environmentally adapted cancer cells was modulated in different ways depending on the drug and the concentration used. High doses of doxorubicin reduced cancer stem cell features, whereas 5‐fluorouracil increased stemness and decreased the proliferative phenotype. By using PDSs repopulated with other breast cancer cell lines, T‐47D and MDA‐MB‐231, we observed both general and cell line specific drug responses. In summary, PDSs can be used to examine the extracellular matrix influence on cancer drug responses and for testing novel compounds in in vivo‐like microenvironments. This article introduces a novel 3D in vivo‐like culture system by using decellularized scaffolds from primary breast cancer samples, which allow to study the influence of the tumor microenvironment in response to chemotherapeutic agents. |
Databáze: | OpenAIRE |
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