A biofabricated 3D cancer-stroma tumor microenvironment model

Area of Science:

• Biomaterials Science
• Cancer Biology
• Cellular Microenvironment Engineering

Background:

• Breast cancer progression involves complex interactions within the tumor microenvironment.
• Existing in vitro models struggle to replicate the multi-cellular dynamics and matrix architecture crucial for studying cancer progression.

Purpose of the Study:

• To develop and validate a microengineered 3D matrix model for studying breast cancer cell and stromal cell interactions.
• To investigate the impact of matrix properties on cancer cell invasion, stromal cell transformation, and drug response.

Main Methods:

• Utilized granular suspension matrices and drop-on-demand bioprinting to create a microporous 3D matrix.
• Integrated breast cancer cells (MCF-7, MDA-MB-231) and adipose-derived stromal cells (ADSCs) within tunable gelatin-methacryloyl microgels.
• Mimicked healthy and fibrotic microenvironments by adjusting matrix porosity and density.

Main Results:

• High-density microgel matrices promoted ADSC transformation into cancer-associated fibroblasts (CAFs).
• ADSC-CAF transformation influenced cancer cell tumorigenicity and chemoresistance markers.
• Doxorubicin treatment enhanced tumorigenicity in co-cultures, highlighting drug effects within the engineered microenvironment.

Conclusions:

• Microengineered matrices provide a powerful platform for studying cell-matrix and cell-cell interactions in cancer.
• This model system has potential for high-throughput screening in biological discovery and drug development for breast cancer.
• Understanding matrix influence on stromal cells and subsequent cancer cell behavior is critical for therapeutic strategies.