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The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues
Published on: June 16, 2018
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A cell-state axis underlying colonization in carcinomas with implications for metastasis risk prediction and
Jesse S Handler1, Zijie Li2, Rachel K Dveirin3
1Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cell Reports
|December 16, 2025
Summary
Researchers identified a new cell-state axis driving pancreatic cancer liver metastasis. They developed MetScore, a biomarker predicting patient outcomes and identifying c-Fos as a potential anti-metastatic target.
Area of Science:
- Oncology
- Cancer Biology
- Genomics
Background:
- Liver metastasis is a primary driver of mortality in pancreatic ductal adenocarcinoma (PDAC).
- The mechanisms underlying PDAC liver colonization are not fully understood.
- Existing classifications do not fully capture metastatic potential.
Purpose of the Study:
- To elucidate the mechanisms of PDAC liver colonization.
- To identify a novel biomarker for metastatic potential.
- To discover actionable therapeutic targets for pancreatic cancer metastasis.
Main Methods:
- Genomic barcoding was used to create a clonal competition model in mice.
- Transcriptome and chromatin-accessibility analyses identified a "metastatic-potential axis".
- MetScore was developed as a biomarker, and functional screening identified c-Fos.
Main Results:
- A distinct "metastatic-potential axis" was identified, separate from other known PDAC axes.
- MetScore effectively distinguishes primary PDAC from metastases and predicts patient outcomes.
- High-MetScore PDAC cells were found in immune cell-rich niches, and c-Fos was identified as a colonization mediator.
Conclusions:
- A novel cell-state axis governs PDAC liver colonization.
- MetScore is a broadly applicable biomarker for metastatic potential across carcinoma subtypes.
- c-Fos is a potential therapeutic target for inhibiting pancreatic cancer metastasis.
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