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Updated: Jan 8, 2026

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues
Published on: June 16, 2018
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.
Abstract:
Metastasis to the liver drives mortality in pancreatic ductal adenocarcinoma (PDAC), yet mechanisms of colonization remain unclear. Using genomic barcoding, we developed a clonal competition model under immune surveillance, isolating murine PDAC subclones with high or low liver-colonization potential. Combined transcriptome and chromatin-accessibility analyses revealed a distinct "metastatic-potential axis," separate from the normal-to-PDAC and classical-basal axes. We established "MetScore" as a biomarker of this axis. MetScore distinguishes metastases from primary PDAC tumors in patients, predicts outcomes beyond classical-basal classifications, and generalizes across carcinoma subtypes, suggesting conserved colonization mechanisms. High-MetScore PDAC cells preferentially occupy immune cell-enriched niches, suggesting they remodel the metastatic microenvironment. Functional screening identified c-Fos as a positive mediator of colonization and a candidate anti-metastatic target. Collectively, we identify a cell-state axis underpinning PDAC liver colonization, introduce MetScore as a broadly applicable biomarker, and nominate actionable targets for peri-operative therapeutic intervention.
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