ODSEI Chip: An Open 3D Microfluidic Platform for Studying Tumor Spheroid-Endothelial Interactions.

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Drug Discovery

Background:

• 3D tumor spheroids are valuable for studying cancer progression and drug response.
• Developing functional vasculature within in vitro tumor models remains a significant challenge for high-throughput analysis.

Purpose of the Study:

• To present a novel open 3D-microarray platform for spheroid-endothelium interaction (ODSEI) studies.
• To investigate the role of vasculature in acquired tamoxifen resistance in breast cancer spheroids.

Main Methods:

• Development of the ODSEI chip for high-throughput arraying of over 1000 spheroids on vasculature.
• Monitoring breast cancer spheroid-vasculature crosstalk and analyzing drug resistance at a single spheroid level.
• Utilizing single-cell RNA sequencing and protein arrays to elucidate molecular mechanisms of resistance.

Main Results:

• Breast cancer spheroids showed reduced tamoxifen sensitivity when co-cultured with vasculature.
• Acquired tamoxifen resistance was linked to the TNF-α pathway via NF-κB and mTOR signaling.
• Targeting identified cytokines (IL-8, TIMP1) reversed tamoxifen resistance in cancer spheroids.

Conclusions:

• The ODSEI chip facilitates the study of spheroid-endothelial interactions for improved tumor biology insights.
• Understanding these interactions can lead to novel therapeutic strategies for overcoming drug resistance.
• The findings highlight the potential of targeting specific cytokines to enhance cancer treatment efficacy.