Investigating breast cancer cell behavior using tissue engineering scaffolds.

Area of Science:

• Biomaterials Science
• Cancer Biology
• Tissue Engineering

Background:

• Breast cancer (BC) remains a clinical challenge due to recurrence, potentially linked to dormant, chemoresistant breast cancer cells (BCCs).
• Current in vitro models (2-D cultures) fail to replicate the in vivo tumor microenvironment, limiting understanding of BCC dormancy.

Purpose of the Study:

• To engineer three-dimensional (3-D) tissue scaffolds that mimic the tumor microenvironment.
• To investigate the effect of these 3-D scaffolds on the behavior of chemoresistant and non-treated breast cancer cells (BCCs).

Main Methods:

• Fabrication of poly (ε-caprolactone) (PCL) fibrous scaffolds with aligned or random fibers to simulate tumor extracellular matrix.
• Induction of chemoresistance in BCCs using carboplatin treatment.
• Analysis of BCC proliferation, viability, cell cycle, and protein expression (Bcl-2, Oct-4, Sox-2, cyclin D1) on scaffolds versus 2-D tissue culture polystyrene (TCP).

Main Results:

• Western blot confirmed increased apoptosis resistance and stem-like markers (Bcl-2, Oct-4, Sox-2) in chemoresistant BCCs.
• Non-treated aggressive BCCs showed reduced proliferation on 3-D scaffolds compared to TCP, indicating dormancy induction.
• Treated BCCs maintained their phenotype on both TCP and scaffolds, while cyclin D1 expression varied, suggesting differential responses to the microenvironment.

Conclusions:

• 3-D PCL scaffolds can induce a dormant phenotype in aggressive breast cancer cells (BCCs).
• The engineered scaffolds provide a more physiologically relevant model for studying BCC dormancy and chemoresistance.
• These findings offer a novel system to explore the 3-D microenvironment's role in breast cancer recurrence and treatment resistance.