Cancers, Vol. 12, Pages 801: Extracellular Protease ADAMTS1 Is Required at Early Stages of Human Uveal Melanoma Development by Inducing Stemness and Endothelial-Like Features on Tumor Cells

Cancers, Vol. 12, Pages 801: Extracellular Protease ADAMTS1 Is Required at Early Stages of Human Uveal Melanoma Development by Inducing Stemness and Endothelial-Like Features on Tumor Cells Cancers doi: 10.3390/cancers12040801 Authors: Peris-Torres Plaza-Calonge López-Domínguez Domínguez-García Barrientos-Durán Carmona-Sáez Rodríguez-Manzaneque Extracellular matrix remodeling within the tumor microenvironment has been recognized as a relevant dynamic framework during tumor growth. However, research on proteases that trigger this remodeling keeps revealing a wide range of actions including both pro- and anti-tumorigenic. The extracellular protease ADAMTS1 exemplifies this dual role. In this work, we first confirmed a positive correlation of ADAMTS1 with endothelial-like phenotype of human melanoma cells together with the finding of associated signatures, including key genes such as endothelial CDH5. Using a CRISPR-Cas9 approach, we observed that the inhibition of ADAMTS1 in an aggressive uveal melanoma model compromised its endothelial-like properties, and more importantly, caused a robust blockade on the progression of tumor xenografts. Although vasculature emerged affected in ADAMTS1-deficient tumors, the most relevant action implied the downregulation of endothelial CDH5 in tumor cells, in association with stemness markers. Indeed, melanoma sphere assays also revealed a deficient commitment to form ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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AbstractPurposeUveal melanoma (UM) is the most common intraocular cancer with a high mortality rate that requires new research in the field of prevention and treatment. c-REL is a member of the nuclear factor κB (NF-κB) transcription factor family and an emerging regulator of tumorigenesis. Therefore, the objective of the study is to evaluate the constitutive expression of c-REL in uveal melanoma patients and its prognostic significance.MethodsDetection of c-REL expression was carried out by immunohistochemistry in all 75 patients, and qRT-PCR performed on 58 fresh cases of uveal melanoma along with IL-6 status...
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
. Parsons Treatment of uveal melanoma (UM) is generally successful, with local primary tumour control being at 90%–95%. Localized radiotherapy in the form of plaque brachytherapy or proton beam radiotherapy is the most common treatment modality in the UK. However, the basic mechanisms of radiation response, DNA repair and tissue reactions in UM have not been well documented previously. We have investigated the comparative radiosensitivity of four UM cell lines in response to exogenous radiation sources (both X-rays and protons), and correlated this with DNA repair protein expression and repair efficiency. We ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Publication date: Available online 22 May 2020Source: Seminars in Cancer BiologyAuthor(s): Prisca Bustamante, Léo Piquet, Solange Landreville, Julia V. Burnier
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Conclusion: The MOLES scoring system is a sensitive (99.8%) tool for indicating malignancy in melanocytic choroidal tumors (MOLES ≥ 3). If the examining practitioner can recognize the five features suggestive of malignancy, MOLES is a safe tool to optimize referral of melanocytic choroidal tumors for specialist care.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
TT, Turunen JA Abstract Uveal melanoma (UM) is a rare intraocular cancer with the highest incidence in Northern latitudes. Metastases develop in approximately 50% of patients whereafter the median survival is 13 months. Generally, the mutation burden of these tumors is low. Germline variants predisposing to UM have been previously described in BRCA1 associated protein 1 (BAP1). Recently, germline and somatic loss-of-function (LOF) variants in the methyl-CpG binding domain-4 (MBD4) gene have been found to cause a hypermutated UM, and MBD4 also has been put forward as a gene predisposing to UM. We sequenced for MBD...
Source: Pigment Cell and Melanoma Research - Category: Cytology Authors: Tags: Pigment Cell Melanoma Res Source Type: research
This study analyzed the immune landscape of adaptive immune resistance signatures and infiltrating immune cells in the TME of UM. Identification of these immune-related biomarkers may thus enable the prediction of prognosis and the selection of optimal immunotherapy strategies in UM. PMID: 32439398 [PubMed - as supplied by publisher]
Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research
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Source: Nutrition and Cancer - Category: Cancer & Oncology Authors: Source Type: research
Abstract Uveal melanoma (UM) is the most common primary intraocular tumour in adults. The most accurate prognostic factor of UM is classification by gene expression profiling. Currently, the role of epigenetics is much less defined compared to genetic mechanisms. We recently showed a strong prognostic role of the expression levels of histone variant macroH2A1 in UM patients. Here, we assessed the mechanistic effects of macroH2A1 on UM progression.UM cell lines were stably knocked down (KD) for macroH2A1, and proliferation and colony formation capacity were evaluated. Mitochondrial function was assayed through qPCR...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
Abstract BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that has long been considered to be a tumor suppressor in various tumors, including renal cell carcinoma, uveal melanoma, mesothelioma, and cutaneous melanoma. However, the involvement of BAP1 in the progression of prostate cancer has not been studied until recently. Herein, we investigated the tumor promoting function of BAP1 in the context of prostate cancer. Analysis of The Cancer Genome Atlas (TCGA) data set showed that prostate cancer patients express high levels of BAP1 mRNA. High BAP1 expression is inversely correlated with disease-free survival...
Source: Genetics and Molecular Biology - Category: Genetics & Stem Cells Source Type: research
In this study, we sought to identify microRNAs (miRNAs) associated with metastasis and OS in UM. We analyzed the miRNA expression and clinical outcomes data from The Cancer Genome Atlas (TCGA) dataset for UM. Differential expression analyses were conducted for each miRNA with respect ever-development of metastasis. Multiple survival analyses were done, using the Cox proportional hazards model, to evaluate interactions between miRNA expression, metastasis, and OS. A total of 22 miRNAs (3 upregulated and 19 downregulated) were differentially expressed between patients with vs. without metastatic UM. These 22 miRNAs could be ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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