ArticleInvestigative ophthalmology & visual science2025
Characterization of Early Metastatic Subpopulations in Uveal Melanoma: Single-Cell Insights Into SPP1+ Cells and Their Interactions With Macrophages.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Multi-omics data reveal B cell regulated immune heterogeneity of MIF signaling pathway in uveal melanoma.Cancer cell international · 2026Article
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13 authors.
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Abstract
Purpose: To identify highly invasive subpopulations of tumor cells that may be responsible for early uveal melanoma (UM) metastasis at the single-cell level and to analyze their interactions with immune cells. Methods: Single-cell RNA sequencing was conducted on 11 samples from 11 UM patients who underwent primary enucleation. The patients were categorized into metastasis (M+) and nonmetastasis (M-) groups based on whether metastasis occurred during the 3-year follow-up. The results were validated using bulk RNA sequencing data from 133 patients from our cohort (n = 53) and The Cancer Genome Atlas human UM database (n = 80). The clustering was confirmed by immunofluorescence. Cell proliferation and invasiveness were evaluated using CCK8 and transwell assays. Apoptosis was analyzed using flow cytometry after Annexin V-fluorescein isothiocyanate/propidium iodide staining. The relative expression levels of genes were assessed using RT-qPCR. Results: A secreted phosphoprotein 1 (SPP1)+ cluster that may be related to early metastasis and high invasiveness was identified by comprehensive bioinformatics analysis and confirmed by immunofluorescence in UM sections. In vitro experiments supported that SPP1 regulates UM cell proliferation, migration, and invasion. Moreover, C-C motif chemokine ligand 3+ (CCL3+) macrophages were associated with poor prognosis, and the high mobility group box 1/T cell immunoglobulin and mucin domain-containing protein 3 (HMGB1/TIM-3) axis may serve as a potential immune checkpoint target. Consequently, SPP1+ melanoma cell populations will likely interact with CCL3+ macrophages, highlighting their possible role in the metastatic process. Conclusions: Our study reveals early metastatic mechanisms in UM by identifying highly invasive SPP1+ melanoma cells and their interaction with macrophages, providing potential therapeutic targets for the metastatic process.
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