EMT and Back Again: Visualizing the Dynamic Phenotypes of Metastasis

Area of Science:

• Cancer Biology
• Cellular Dynamics
• Metastasis Research

Background:

• The role of epithelial-to-mesenchymal transition (EMT) in tumor metastasis remains a significant, debated question in cancer research.
• Previous studies using lineage tracing suggested limited contribution of EMT to metastasis, but questions about marker concordance persisted.

Purpose of the Study:

• To investigate the extent to which tumor cells acquiring mesenchymal phenotypes contribute to the metastatic process.
• To provide a granular view of phenotypic transitions during metastasis and their heterogeneity.

Main Methods:

• Utilized fluorescence-based lineage tracing technology.
• Complemented lineage tracking with single-cell analysis for a detailed phenotypic assessment.

Main Results:

• Evidence suggests very few cells within experimental metastases undergo a complete epithelial-to-mesenchymal transition.
• Single-cell analysis revealed striking heterogeneity in phenotypic transitions during metastasis.
• Marker conversion may not always accurately reflect true cellular phenotypic state during metastasis.

Conclusions:

• The acquisition of mesenchymal phenotypes via EMT appears to play a limited role in the formation of experimental metastases.
• Metastasis involves a heterogeneous mix of cellular phenotypes, underscoring the complexity of the process.
• Single-cell analysis is crucial for accurately characterizing cellular plasticity during tumor progression and metastasis.