Probing 3D Collective Cancer Invasion Using Double-Stranded Locked Nucleic Acid Biosensors

Area of Science:

• Cancer Biology
• Molecular Diagnostics
• Biotechnology

Background:

• Metastasis accounts for over 90% of cancer deaths, highlighting the need for anti-invasion therapies.
• Understanding cancer invasion in 3D microenvironments is crucial but limited by a lack of effective monitoring tools.
• Current methods struggle to dynamically analyze gene expression and biomechanical interactions during 3D invasion.

Purpose of the Study:

• To develop and utilize a novel biosensor for investigating 3D collective cancer invasion.
• To dynamically analyze single-cell gene expression during invasion in a 3D microenvironment.
• To characterize biomechanical interactions between invading cancer cells and the extracellular matrix.

Main Methods:

• Development of a double-stranded locked nucleic acid (dsLNA) biosensor.
• Integration of the dsLNA biosensor with multiphoton microscopy.
• Dynamic single-cell gene expression analysis and biomechanical characterization of 3D cancer invasion.

Main Results:

• The dsLNA biosensor successfully enabled dynamic monitoring of 3D collective cancer invasion.
• Gene profiling identified distinct signaling mechanisms in invasive leader cells versus detached cells.
• Notch signaling was identified as a key pathway involved in 3D collective cancer invasion.

Conclusions:

• The dsLNA biosensor is a powerful tool for studying 3D cancer invasion dynamics and gene expression.
• Distinct cellular mechanisms govern collective versus individual invasion in 3D microenvironments.
• Targeting Notch signaling presents a potential therapeutic strategy for antimetastasis treatments.