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Modeling Breast Cancer in Human Breast Tissue using a Microphysiological System
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Modeling Breast Cancer in Human Breast Tissue using a Microphysiological System.

Loren M Brown1, Katherine L Hebert2, Rakesh R Gurrala3

  • 1Department of Surgery, Louisiana State University Health Sciences Center.

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|May 10, 2021
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Summary

New breast cancer models (BC-MPS) use human tissue to study disease progression and drug response. This advanced system better mimics the tumor microenvironment for improved research and therapeutic development.

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Area of Science:

  • Biomedical Engineering
  • Cancer Biology
  • Microphysiological Systems

Background:

  • Breast cancer (BC) is a leading cause of mortality in women, with high drug failure rates in clinical trials.
  • Existing research models inadequately represent the complex tumor microenvironment, hindering therapeutic translation.
  • The NIH Microphysiological Systems (MPS) program aims to bridge this gap by developing advanced in vitro models.

Purpose of the Study:

  • To develop and validate a novel breast cancer microphysiological system (BC-MPS) using primary human tissues.
  • To create a more biologically relevant model for studying breast cancer progression and its microenvironment.
  • To investigate breast cancer cell motility and metabolic crosstalk within this new model.

Main Methods:

  • Adapted a method of culturing white adipose tissue (WAT) between adipose-derived stem cell (ASC) sheets.
  • Incorporated breast cancer cells into non-diseased human breast tissue (HBT) with native microenvironment components.
  • Sandwiched the breast cancer-human breast tissue admixture between HBT-derived ASC sheets for ex vivo culture.

Main Results:

  • The developed BC-MPS model remained stable in culture ex vivo for at least 14 days.
  • The model successfully recapitulated key breast cancer behaviors, including cell motility and metabolic crosstalk.
  • Demonstrated high-resolution, time-lapse imaging of BC motility and the first in vitro demonstration of metabolic crosstalk between primary human mammary adipocytes and BC cells.

Conclusions:

  • BC-MPS provides a stable, biologically relevant platform for studying breast cancer in its native microenvironment.
  • This model system enhances the study of breast cancer cell interactions with stromal and immune cells.
  • BC-MPS offers a promising tool for improving the clinical translation of breast cancer research and drug development.