JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Development and characterisation of a novel 3D in vitro model of obesity-associated breast cancer as a tool for drug testing

  • 0Antibody and Vaccine Group, Centre for Cancer Immunology, School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, UK.
Npj Breast Cancer +

|

May 30, 2025

|

May 30, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Obesity worsens breast cancer outcomes and reduces treatment effectiveness. A new 3D model shows obese tumors are more sensitive to metformin but resistant to paclitaxel, aiding therapy resistance research.

Area Of Science

  • Oncology
  • Cancer Biology
  • Tumor Microenvironment Research

Background

  • Obesity is linked to poorer breast cancer prognosis and reduced treatment efficacy.
  • Mechanisms of obesity-driven therapy resistance are not fully understood due to inadequate models.
  • A need exists for models that accurately represent the obese tumor microenvironment.

Purpose Of The Study

  • To develop and validate a novel 3D in vitro model of obesity-associated breast cancer.
  • To investigate biological mechanisms driving therapy resistance in an obese context.
  • To establish a drug testing platform for obesity-related breast cancer.

Main Methods

  • A penta-culture system was created using adipocyte spheroids, breast tumor cells, myoepithelial cells, macrophages, and fibroblasts within a collagen matrix.
  • The model recapitulated the inflamed-adipose border observed in obese patients through tumor cell and macrophage infiltration of adipocyte spheroids.
  • The model's utility as a drug testing platform was evaluated.

Main Results

  • The 3D organotypic model successfully mimicked key features of the obese adipose tumor microenvironment.
  • Obese cultures demonstrated increased sensitivity to metformin compared to non-obese cultures.
  • Conversely, obese cultures exhibited resistance to paclitaxel when compared to non-obese cultures.

Conclusions

  • This 3D organotypic model effectively replicates the obese adipose tumor microenvironment.
  • The model serves as a valuable tool for exploring the mechanisms of obesity-related therapy resistance.
  • Findings suggest differential drug responses in obese breast cancer models warranting further investigation.