ArticleBiomarker research2024
Detection of neoplastic-immune hybrid cells with metastatic properties in uveal melanoma.
Article in Biomarker research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- A Circulating Signature of Tumour Hybrid Cells and Immune Checkpoints Predicts Metastatic Progression in Lung Cancer.International journal of molecular sciences · 2026Article
- Neoplastic Immune Mimicry Potentiates Breast Tumor Progression.Cancer research · 2026Article
- The double-positive cells in the tumor microenvironment.Journal of translational internal medicine · 2026Article
- Isolation and typing techniques for circulating tumor cells.Biomarker research · 2026Review
- Cell-Cell Fusion as a Mechanism of Immune Evasion and Metastatic Progression.Advances in experimental medicine and biology · 2026Review
- Implications of Heterotypic Cell Fusion in Cancer.Advances in experimental medicine and biology · 2026Review
- Single-cell RNA-sequencing of circulating tumour cells: A practical guide to workflow and translational applications.Cancer metastasis reviews · 2025Review
- Clinical applications of circulating tumor cells in metastasis and therapy.Journal of hematology & oncology · 2025Review
- Circulating tumor cells: Blood-based detection, molecular biology, and clinical applications.Cancer cell · 2025Review
- Article
- Epidemiology and tumor microenvironment of ocular surface and orbital tumors on growth and malignant transformation.Frontiers in oncology · 2024Review
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14 authors.
Funding
Abstract
backgroundUveal melanoma is the most common non-cutaneous melanoma and is an intraocular malignancy affecting nearly 7,000 individuals per year worldwide. Of these, approximately 50% will progress to metastatic disease for which there are currently no effective curative therapies. Despite advances in molecular profiling and metastatic stratification of uveal melanoma tumors, little is known regarding their underlying biology of metastasis. Our group has identified a disseminated neoplastic cell population characterized by co-expression of immune and melanoma proteins, circulating hybrid cells (hybrids), in patients with uveal melanoma. Compared to circulating tumor cells, which lack expression of immune proteins, hybrids are detected at an increased prevalence in peripheral blood and can be used as a non-invasive biomarker to predict metastatic progression.
methodsTo ascertain mechanisms underlying enhanced hybrid cell dissemination we identified hybrid cells within primary uveal melanoma tumors using single cell RNA sequencing (n = 8) and evaluated their gene expression and predicted ligand-receptor interactions in relation to other melanoma and immune cells within the primary tumor. We then verified expression of upregulated hybrid pathways within patient-matched tumor and peripheral blood hybrids (n = 4) using cyclic immunofluorescence and quantified their protein expression relative to other non-hybrid tumor and disseminated tumor cells.
resultsAmong the top upregulated genes and pathways in hybrid cells were those involved in enhanced cell motility and cytoskeletal rearrangement, immune evasion, and altered cellular metabolism. In patient-matched tumor and peripheral blood, we verified gene expression by examining concordant protein expression for each pathway category: TMSB10 (cell motility), CD74 (immune evasion) and GPX1 (metabolism). Both TMSB10 and GPX1 were expressed on significantly higher numbers of disseminated hybrid cells compared to circulating tumor cells, and CD74 and GPX1 were expressed on more disseminated hybrids than tumor-resident hybrids. Lastly, we identified that hybrid cells express ligand-receptor signaling pathways implicated in promoting metastasis including GAS6-AXL, CXCL12-CXCR4, LGALS9-P4HB and IGF1-IGFR1.
conclusionThese findings highlight the importance of TMSB10, GPX1 and CD74 for successful hybrid cell dissemination and survival in circulation. Our results contribute to the understanding of uveal melanoma tumor progression and interactions between tumor cells and immune cells in the tumor microenvironment that may promote metastasis.
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