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Mammary Epithelial and Endothelial Cell Spheroids as a Potential Functional In vitro Model for Breast Cancer Research
Published on: July 12, 2021
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Characterization of multicellular breast tumor spheroids using image data-driven biophysical mathematical modeling
Haley J Bowers1,2, Emily E Fannin1, Alexandra Thomas3,4
1Department of Biomedical Engineering, Wake Forest School of Medicine, 575 N. Patterson Ave., Suite 530, Winston-Salem, NC, 27101, USA.
Scientific Reports
|July 16, 2020
Summary
This study introduces a new computational model to analyze multicellular tumor spheroids (MCTS) in cancer research. The framework accurately measures tumor growth and drug effects, outperforming traditional methods for evaluating antineoplastic drugs.
Area of Science:
- Biophysics
- Cancer Biology
- Computational Biology
Background:
- Multicellular tumor spheroids (MCTS) are advanced in vitro models simulating solid tumors and their microenvironments.
- Current methods for assessing MCTS growth and drug efficacy often lack precision and mechanistic insight.
- There is a need for sophisticated analytical tools to better understand tumor behavior and treatment responses in 3D cell cultures.
Purpose of the Study:
- To develop and validate a coupled experimental-computational framework for estimating phenotypic growth and biophysical properties of MCTS.
- To mechanistically characterize MCTS using standard microscopy and advanced mathematical modeling.
- To assess the efficacy of antineoplastic drugs by analyzing changes in MCTS biophysical parameters.
Main Methods:
- A novel microscopy image processing framework was developed, extending a previous in vivo mechanically-coupled reaction-diffusion model.
- The framework integrates standard microscopy imaging with a biophysical mathematical model to analyze MCTS growth and mechanical interactions.
- Biophysical parameters including cellular diffusion, proliferation rate, and traction forces were estimated for MDA-MB-231 breast cancer MCTS.
Main Results:
- The computational framework successfully estimated key biophysical parameters of MCTS.
- Significant differences in cellular diffusion, proliferation, and traction forces were observed between treated and untreated MCTS over time.
- These model-derived parameters provided more conclusive results than traditional size-based morphometric analyses.
Conclusions:
- The coupled experimental-computational framework offers a powerful tool for mechanistic characterization of MCTS.
- This approach enables more precise assessment of in vitro drug efficacy compared to conventional methods.
- The developed computational methodologies for 3D cell culture systems hold significant potential for improving antineoplastic drug development and evaluation.
