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Updated: Jul 5, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Comparison of Human Melanoma Single Cell Profiles to Evolutionary Medicine Model Xiphophorus Provides Insights in
Yuan Lu1, Will Boswell1, Rachel Carroll2
1Institute for Molecular Life Sciences, Texas State University, San Marcos, Texas, USA.
Abstract:
Melanoma remains one of the deadliest forms of cancer. Despite recent therapeutic advances, including immune checkpoint inhibitors and small-molecule kinase inhibitors, patients frequently develop treatment resistance. Novel models are needed to devise strategies that overcome resistance and further reduce melanoma-related mortality. Interspecies hybrid fish from the Xiphophorus lineage develop mutant Epidermal Growth Factor Receptor (EGFR)-driven melanomas that display morphology, bulk gene expression, disease initiation, and progression processes mimicking those of human melanomas. These similarities have enabled their comparative use in evaluating why human melanomas exhibit cancer cell plasticity and how the cancer cells interact with diverse immune populations. However, it remains unclear whether Xiphophorus melanomas recapitulate some or all these features. To address this, we performed single-nucleus RNA sequencing (snRNAseq) analysis of Xiphophorus melanomas. Employing comparative analyses with results from human melanoma studies, we demonstrate that Xiphophorus melanomas faithfully mimic the cellular heterogeneity observed in human melanoma, including cancer cells, endothelial cells, cancer-associated fibroblasts, B cells, M1 and M2 macrophages, N1 and N2 neutrophils, various T helper cells, and less cytotoxic, but not exhausted CD8+ T cells. Immune and cancer cell subtyping showed Xiphophorus melanoma represented an immune-evaded status.
Insights
Xiphophorus fish develop melanomas that mimic human cancer. Single-nucleus RNA sequencing reveals these fish models accurately reflect human melanoma
Area of Science:
- Oncology
- Comparative Pathology
- Genomics
Background:
- Melanoma is a deadly cancer with frequent treatment resistance.
- Novel models are crucial for understanding resistance and reducing mortality.
- Xiphophorus fish develop melanomas resembling human disease.
Purpose of the Study:
- To validate Xiphophorus melanomas as accurate models for human melanoma.
- To investigate cellular and immune heterogeneity in Xiphophorus melanomas.
- To compare Xiphophorus melanoma characteristics with human melanoma studies.
Main Methods:
- Single-nucleus RNA sequencing (snRNAseq) of Xiphophorus melanomas.
- Comparative analysis with human melanoma snRNAseq data.
- Immune and cancer cell subtyping.
Main Results:
- Xiphophorus melanomas exhibit cellular heterogeneity mirroring human melanoma.
- Key cell types, including cancer cells and immune cells, were identified.
- The study identified an immune-evaded status in Xiphophorus melanoma.
Conclusions:
- Xiphophorus melanomas are a faithful model for human melanoma.
- This model can advance research into melanoma plasticity and immune interactions.
- Findings support the use of Xiphophorus for developing strategies against melanoma resistance.
