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- Title
Circulating tumor cells from melanoma patients show phenotypic plasticity and metastatic potential in xenograft NOD.CB17 mice.
- Authors
Felici, Claudia; Mannavola, Francesco; Stucci, Luigia Stefania; Duda, Loren; Cafforio, Paola; Porta, Camillo; Tucci, Marco
- Abstract
<bold>Background: </bold>Innovative therapies have improved the overall survival in melanoma, although a high number of patients still experience disease progression or recurrence. Ex-vivo culture of circulating tumour cells (CTCs) represents a valuable laboratory resource for in-depth characterization of rare cell populations responsible for disease progression.<bold>Methods: </bold>CTCs from patients with metastatic melanoma were in-vitro established. Their stemness was demonstrated by both phenotypic and genotypic assays, as well as by functional studies. Xenograft experiments in NOD.CB17 mice injected with CTCs from a single patient were completed. Data were analysed by Student's test and results expressed as mean ± SEM.<bold>Results: </bold>CTCs share the mutational profile with primary cells, an intermediate epithelial-mesenchymal transition (EMT) phenotype and high expression of the immunosuppressive factors. A subclonal CTC population exhibited stem cell properties as high aldehyde dehydrogenase 1 activity, melanosphere-forming ability, and expression of major stemness transcription factors. Xenograft experiments confirmed the CTC ability to generate melanoma in-vivo and revealed enhanced metastatic propensity.<bold>Conclusions: </bold>CTCs play a relevant role in melanoma and may actively contribute to drive the disease progression and metastasis. Thus, they are a unique potential tool for pharmacogenomic studies to guide treatment strategies in advanced disease.
- Subjects
DISEASE progression; XENOGRAFTS; MELANOMA; ANIMAL experimentation; METASTASIS; PHYSIOLOGICAL adaptation; MICE
- Publication
BMC Cancer, 2022, Vol 22, Issue 1, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-022-09829-1