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
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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