A NAMs-Based Microphysiological System for Metastasis and Mechanobiology Studies

Area of Science:

• Oncology
• Biotechnology
• Translational Medicine

Background:

• Lung cancer is a leading cause of cancer death, frequently metastasizing to bone.
• The tumor microenvironment, including the extracellular matrix and epithelial-mesenchymal transition (EMT), is critical in lung cancer progression and metastasis.
• Existing 2D and animal models inadequately replicate complex tumor-bone interactions.

Purpose of the Study:

• To develop and validate a physiologically relevant in vitro "lung cancer metastasis-on-a-chip" platform.
• To model lung cancer cell metastasis to the bone microenvironment.
• To study epithelial-mesenchymal transition (EMT) dynamics in lung cancer metastasis.

Main Methods:

• A dual-chamber microfluidic device simulating lung and bone compartments.
• Integration of lung cancer cells and human osteoblasts within the chip.
• Utilized time-lapse microscopy, ELISA, and qRT-PCR to analyze cellular dynamics, protein secretion, and gene expression.

Main Results:

• The platform successfully demonstrated lung cancer cell metastasis to the bone compartment.
• Observed disruption of the bone microenvironment and increased mesenchymal markers.
• Detected upregulation of epithelial proliferation markers in the lung compartment, indicating simultaneous primary tumor dissemination and secondary site colonization.

Conclusions:

• The metastasis-on-a-chip platform accurately mimics in vivo lung cancer metastasis to bone.
• This model provides a valuable tool for studying tumor-bone interactions and EMT.
• The platform supports exposome research in oncology, advancing precision medicine and reducing animal testing.