Development of a Novel 3D Tumor-tissue Invasion Model for High-throughput, High-content Phenotypic Drug Screening

Area of Science:

• Oncology
• Biomedical Engineering
• Drug Discovery

Background:

• Invasive cancers like pancreatic cancer are difficult to treat due to limitations in current preclinical models.
• Existing 3D spheroid invasion models lack reproducibility and automation for high-throughput screening.
• Predictive preclinical models are crucial for improving anti-cancer drug development and clinical trial success rates.

Purpose of the Study:

• To develop a novel, reproducible 3D tumor-tissue invasion model for studying invasive cancer phenotypes.
• To create a model that interfaces with automated systems for high-throughput drug screening.
• To enhance the pathophysiological relevance of preclinical cancer models.

Main Methods:

• A custom fabrication system was used to create high-cell density tumor compartments.
• Standardized oligomeric type I collagen was employed to modulate extracellular matrix properties.
• Low-passage, patient-derived pancreatic cancer cells and cancer-associated fibroblasts were utilized.

Main Results:

• The novel 3D model demonstrated reproducible setup and user-defined tumor and tissue compartments.
• Pancreatic cancer cell lines exhibited differential invasive phenotypes within the model.
• Fibroblast-mediated tumor invasion and matrix alignment were observed, increasing pathophysiological relevance.
• A proof-of-concept multiplex drug screening assay was successfully applied, demonstrating the model's potential for automated, high-content screening.

Conclusions:

• The developed 3D tumor-tissue invasion model addresses limitations of existing models, offering improved reproducibility and automation.
• This model enhances pathophysiological relevance by incorporating patient-derived cells and fibroblasts.
• The model shows significant potential as a predictive tool for high-throughput, high-content anti-cancer drug screening.