A Droplet Microfluidic Approach to Investigate How Fibroblasts Alter Collagen I Spatial Distribution and Endocrine...

Area of Science:

• Oncology
• Biomedical Engineering
• Cell Biology

Background:

• Therapeutic resistance in breast cancer is a major challenge, with the tumor microenvironment (TME) playing a key role.
• Stromal cells, particularly fibroblasts, significantly influence cancer progression through extracellular matrix (ECM) remodeling.
• Understanding tumor-stromal interactions is crucial for developing effective breast cancer treatments.

Purpose of the Study:

• To develop and validate a microfluidic droplet-based 3D coculture platform for studying breast cancer-fibroblast interactions.
• To investigate the impact of fibroblast-mediated stromal remodeling on estrogen receptor-positive (ER+) breast cancer response to endocrine therapy.

Main Methods:

• Development of a microfluidic droplet-based 3D coculture system for uniform breast cancer-fibroblast models.
• Coculturing ER+ breast cancer cells with primary or immortalized fibroblasts.
• Evaluation of Collagen I and Ki67 expression after endocrine therapy exposure.

Main Results:

• Distinct Collagen I 'hotspot' patterns (single reduced vs. multiple increased) observed with primary fibroblasts, independent of spheroid size.
• Coculture with immortalized fibroblasts showed similar patterns but higher overall Collagen I levels.
• Increased Ki67 and Collagen I expression in coculture spheroids during endocrine therapy indicated fibroblast-driven proliferation and modulated response.

Conclusions:

• The developed 3D microfluidic model is effective for probing tumor-stromal interactions in breast cancer.
• Fibroblasts contribute to cancer cell proliferation and influence endocrine therapy response through ECM remodeling.
• This platform provides a foundation for mechanistic studies on ECM-mediated remodeling in breast cancer treatment resistance.