Dataset Information

Circulating tumor cells from melanoma patients show phenotypic plasticity and metastatic potential in xenograft NOD.CB17 mice.

ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

SUBMITTER: Felici C

PROVIDER: S-EPMC9275157 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Circulating tumor cells from melanoma patients show phenotypic plasticity and metastatic potential in xenograft NOD.CB17 mice.

Felici Claudia C Mannavola Francesco F Stucci Luigia Stefania LS Duda Loren L Cafforio Paola P Porta Camillo C Tucci Marco M

BMC cancer 20220711 1

<h4>Background</h4>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.<h4>Methods</h4>CTCs from patients with metastatic melanoma were in-vitro established. Their stemness was demonstrated by both phenotypic and ...[more]

PMID: 35820816

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Project description:BackgroundAbout 20% of patients diagnosed with endometrial cancer (EC) are considered high-risk with unfavorable prognosis. In the framework of the European Network for Individualized Treatment in EC (ENITEC), we investigated the presence and phenotypic features of Circulating Tumor Cells (CTC) in high-risk EC patients.MethodsCTC isolation was carried out in peripheral blood samples from 34 patients, ranging from Grade 3 Stage IB to Stage IV carcinomas and recurrences, and 27 healthy controls using two methodologies. Samples were subjected to EpCAM-based immunoisolation using the CELLection™ Epithelial Enrich kit (Invitrogen, Dynal) followed by RTqPCR analysis. The phenotypic determinants of endometrial CTC in terms of pathogenesis, hormone receptor pathways, stem cell markers and epithelial to mesenchymal transition (EMT) drivers were asked. Kruskal-Wallis analysis followed by Dunn's post-test was used for comparisons between groups. Statistical significance was set at p?<?0.05.ResultsEpCAM-based immunoisolation positively detected CTC in high-risk endometrial cancer patients. CTC characterization indicated a remarkable plasticity phenotype defined by the expression of the EMT markers ETV5, NOTCH1, SNAI1, TGFB1, ZEB1 and ZEB2. In addition, the expression of ALDH and CD44 pointed to an association with stemness, while the expression of CTNNB1, STS, GDF15, RELA, RUNX1, BRAF and PIK3CA suggested potential therapeutic targets. We further recapitulated the EMT phenotype found in endometrial CTC through the up-regulation of ETV5 in an EC cell line, and validated in an animal model of systemic dissemination the propensity of these CTC in the accomplishment of metastasis.ConclusionsOur results associate the presence of CTC with high-risk EC. Gene-expression profiling characterized a CTC-plasticity phenotype with stemness and EMT features. We finally recapitulated this CTC-phenotype by over-expressing ETV5 in the EC cell line Hec1A and demonstrated an advantage in the promotion of metastasis in an in vivo mouse model of CTC dissemination and homing.

Dataset Information

Circulating tumor cells from melanoma patients show phenotypic plasticity and metastatic potential in xenograft NOD.CB17 mice.

Background

Methods

Results

Conclusions

Publications

Circulating tumor cells from melanoma patients show phenotypic plasticity and metastatic potential in xenograft NOD.CB17 mice.

Similar Datasets

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