&lt;p&gt;Research Progress of Cancer Stem Cells in Uveal Melanoma&lt;/p&gt;

Chen, Yu Ning; Li, Yang; Wei, Wen Bin

doi:10.2147/ott.s284262

Cited by 5 publications

(2 citation statements)

References 57 publications

(78 reference statements)

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“…Only a few studies have investigated the role of cancer stem cells in UM. Universally recognized markers of melanoma stem cells are lacking, while their pathways are far from being fully characterized ( 98 ). Though class 1 tumors show similarity to more mature neural crest cells and differentiated melanocytes, class 2 tumors are transcriptionally similar to primitive neural and ectodermal stem cells.…”

Section: Genomic Abnormalities In Uveal Melanomamentioning

confidence: 99%

Genetic Basis and Molecular Mechanisms of Uveal Melanoma Metastasis: A Focus on Prognosis

Gallenga

Franco

Adamo³

et al. 2022

Front. Oncol.

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Uveal melanoma (UM) is the most frequently found primary intraocular tumor, although it accounts for only 5% of all melanomas. Despite novel systemic therapies, patient survival has remained poor. Indeed, almost half of UM patients develop metastases from micro-metastases which were undetectable at diagnosis. Genetic analysis is crucial for metastatic risk prediction, as well as for patient management and follow-up. Several prognostic parameters have been explored, including tumor location, basal dimension and thickness, histopathologic cell type, vascular mimicry patterns, and infiltrating lymphocytes. Herein, the Authors review the available literature concerning cytogenetic prognostic markers and biochemical pathways correlated to UM metastasis development.

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Section: Genomic Abnormalities In Uveal Melanomamentioning

confidence: 99%

Genetic Basis and Molecular Mechanisms of Uveal Melanoma Metastasis: A Focus on Prognosis

Gallenga

Franco

Adamo³

et al. 2022

Front. Oncol.

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“…Recently, CSCs have also been identified in UM as a subgroup of cells characterized by increased motility, self-renewal, and chemoresistance [ 35 – 37 ]. Given the absence of reliable surface markers for CSCs in UM [ 38 ], current studies assessed their presence by evaluating stem-like properties such as formation of melanospheres and enhanced activity of aldehyde dehydrogenase (ALDH) enzymes [ 37 , 39 – 42 ].…”

Section: Introductionmentioning

confidence: 99%

FGF-trapping hampers cancer stem-like cells in uveal melanoma

et al. 2023

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Background Cancer stem-like cells (CSCs) are a subpopulation of tumor cells responsible for tumor initiation, metastasis, chemoresistance, and relapse. Recently, CSCs have been identified in Uveal Melanoma (UM), which represents the most common primary tumor of the eye. UM is highly resistant to systemic chemotherapy and effective therapies aimed at improving overall survival of patients are eagerly required. Methods Herein, taking advantage from a pan Fibroblast Growth Factor (FGF)-trap molecule, we singled out and analyzed a UM-CSC subset with marked stem-like properties. A hierarchical clustering of gene expression data publicly available on The Cancer Genome Atlas (TCGA) was performed to identify patients’ clusters. Results By disrupting the FGF/FGF receptor (FGFR)-mediated signaling, we unmasked an FGF-sensitive UM population characterized by increased expression of numerous stemness-related transcription factors, enhanced aldehyde dehydrogenase (ALDH) activity, and tumor-sphere formation capacity. Moreover, FGF inhibition deeply affected UM-CSC survival in vivo in a chorioallantoic membrane (CAM) tumor graft assay, resulting in the reduction of tumor growth. At clinical level, hierarchical clustering of TCGA gene expression data revealed a strong correlation between FGFs/FGFRs and stemness-related genes, allowing the identification of three distinct clusters characterized by different clinical outcomes. Conclusions Our findings support the evidence that the FGF/FGFR axis represents a master regulator of cancer stemness in primary UM tumors and point to anti-FGF treatments as a novel therapeutic strategy to hit the CSC component in UM.

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Spheroid-induced heterogeneity and plasticity of uveal melanoma cells

Chen

Gao

et al. 2022

Cell Oncol.

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Purpose The mechanism underlying cancer heterogeneity and plasticity remains elusive, in spite of the fact that multiple hypotheses have been put forward. We intended to clarify this heterogeneity in uveal melanoma (UM) by looking for evidence of cancer stem cell involvement and a potential role of ZEB1 in cancer cell plasticity. Methods Spheroids derived from human UM cells as well as xenograft tumors in nude mice were dissected for signs of heterogeneity and plasticity. Two human UM cell lines were studied: the epithelioid type C918 cell line and the spindle type OCM1 cell line. We knocked down ZEB1 in both cell lines to investigate its involvement in the regulation of stem-like cell formation and vascularization by qRT-PCR, immunohistochemistry, flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. Results We found that a small side population (SP) in OCM1 showed stem cell-like properties such as heterogeneity, remote dissemination and nuclear dye exclusion after spheroid formation in vitro. ZEB1 regulated UM stem cell generation indirectly by promoting cell proliferation to form large size tumors in vivo and spheroid in vitro, and directly by binding to stemness genes such as TERT and ABCB1. In addition, we found that ZEB1 participates in vasculogenic mimicry system formation through the regulation of CD34 and VE-cadherin expression. Conclusions From our data we conclude that cancer stem cells may contribute to UM heterogeneity and plasticity and that ZEB1 may play a regulatory role in it.

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<p>Research Progress of Cancer Stem Cells in Uveal Melanoma</p>

Cited by 5 publications

References 57 publications

Genetic Basis and Molecular Mechanisms of Uveal Melanoma Metastasis: A Focus on Prognosis

Genetic Basis and Molecular Mechanisms of Uveal Melanoma Metastasis: A Focus on Prognosis

FGF-trapping hampers cancer stem-like cells in uveal melanoma

Spheroid-induced heterogeneity and plasticity of uveal melanoma cells

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