Invasive three-dimensional organotypic neoplasia from multiple normal human epithelia

Area of Science:

• Oncology
• Biotechnology
• Tissue Engineering

Background:

• Developing clinically relevant cancer models is crucial for evaluating novel therapeutics.
• Existing models often lack the complexity and rapid turnaround time needed for target assessment.

Purpose of the Study:

• To engineer a three-dimensional (3D) human tissue cancer model that recapitulates key features of tumor progression.
• To establish a platform for rapid screening of cancer therapeutics and identification of clinically relevant gene signatures.

Main Methods:

• Primary human epithelial cells from various sites were transformed using tumor-associated genetic pathways within a 3D tissue environment.
• The engineered organotypic tissues incorporated cell-populated stroma and intact basement membranes.
• Gene expression profiles were analyzed and compared between 3D models and spontaneous human cancers.

Main Results:

• Engineered tissues exhibited natural tumor progression features, including basement membrane invasion, potentiated by stromal cells.
• Oncogenic signaling in 3D models closely resembled gene expression profiles of spontaneous human cancers, unlike 2D cultures.
• Screening of 3D organotypic neoplasia with pathway inhibitors identified a clinically faithful cancer gene signature.

Conclusions:

• Multitissue 3D human tissue cancer models offer an efficient and relevant complement to existing cancer research approaches.
• These models facilitate the assessment of numerous potential cancer therapeutic targets in a biologically accurate context.
• The developed models show promise for accelerating cancer drug discovery and development.