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Updated: Feb 6, 2026

A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery
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A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery

Published on: February 28, 2020

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Tumor-stroma interactions differentially alter drug sensitivity based on the origin of stromal cells

Benjamin D Landry1, Thomas Leete1, Ryan Richards1

  • 1Program in Systems Biology, Program in Molecular Medicine, Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.

Molecular Systems Biology
|August 8, 2018
PubMed

Insights

Tumor-stroma interactions significantly impact cancer drug response. Fibroblasts, key stromal cells, can either increase or decrease drug sensitivity in breast cancer cells, revealing new therapeutic targets.

Area of Science:

  • Oncology
  • Cell Biology
  • Cancer Therapeutics

Background:

  • Tumor heterogeneity necessitates personalized cancer treatments.
  • Current stratification often overlooks the tumor microenvironment, focusing primarily on genomics.
  • Understanding tumor-stroma interactions is crucial for effective drug development.

Purpose of the Study:

  • To investigate the role of the tumor microenvironment, specifically tumor-stroma interactions, in modulating cancer drug sensitivity.
  • To identify specific stromal components and their mechanisms of action in altering drug responses.
  • To explore the diversity of fibroblast-tumor cell interactions and their impact on treatment outcomes.

Main Methods:

  • Large-scale coculture assays were employed to measure drug-induced cell death.
  • Breast cancer cells were cultured in monoculture (2D/3D) and coculture with stromal fibroblasts.
  • Drug sensitivity was assessed across different fibroblast origins and tumor cell subtypes.

Main Results:

  • Chemo-insensitivity in aggressive breast cancer subtypes was observed only when cocultured with stromal fibroblasts, not in monoculture.
  • Fibroblasts exhibited two distinct, divergent mechanisms influencing drug responses, irrespective of the drug used.
  • These fibroblast-mediated effects were linked to the modulation of apoptotic priming in tumor cells.

Conclusions:

  • Tumor-stroma interactions, particularly with fibroblasts, play a critical role in determining cancer drug response.
  • Fibroblast heterogeneity contributes to diverse outcomes in tumor drug sensitivity.
  • These findings reveal novel principles of fibroblast influence on tumor cell apoptosis and suggest new avenues for cancer therapy.
Keywords:
drug sensitivityprecision medicinetriple‐negative breast cancertumor microenvironmenttumor–stroma interaction

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