Breast cancer patient-derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments

J Cell Physiol. 2021 Jun;236(6):4709-4724. doi: 10.1002/jcp.30191. Epub 2020 Dec 23.


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.

Keywords: 3D in vitro culture; breast cancer; chemotherapy; decellularized scaffold; extracellular matrix; tumor microenvironment.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Culture Techniques
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Female
  • Fluorouracil / pharmacology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Paclitaxel / pharmacology*
  • Phenotype
  • Printing, Three-Dimensional
  • Tissue Scaffolds
  • Transcriptome
  • Tumor Microenvironment*


  • Antineoplastic Agents
  • Doxorubicin
  • Paclitaxel
  • Fluorouracil