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The influence of melanoma extracellular vesicles on benign melanocytes, dermal fibroblasts and microvascular endothelial cells.

ABSTRACT: This study investigates the role of PRAME (Preferentially Expressed Antigen in Melanoma), a cancer-testis antigen, in melanoma progression, particularly its function in melanoma-derived extracellular vesicles (EVs) and its impact on benign primary melanocytes (PM), primary fibroblasts(PF) and microvascular endothelial cells (EN).

ORGANISM(S): Homo sapiens

PROVIDER: GSE279329 | GEO | 2024/10/16

REPOSITORIES: GEO

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The influence of melanoma extracellular vesicles on benign melanocytes, dermal fibroblasts and microvascular endothelial cells (part1)

Project description:This study investigates the role of PRAME (Preferentially Expressed Antigen in Melanoma), a cancer-testis antigen, in melanoma progression, particularly its function in melanoma-derived extracellular vesicles (EVs) and its impact on benign primary melanocytes (PM), primary fibroblasts(PF) and microvascular endothelial cells (EN).

2024-10-22 | GSE279511 | GEO

The tumor antigen PRAME is a substrate recognition subunit of a Cul2-based ubiquitin ligase and is associated with active NFY promoters

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The tumor antigen PRAME is a substrate recognition subunit of a Cul2-based ubiquitin ligase and is associated with active NFY promoters

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Gene expression profile of Hodgkin’s lymphoma cells after knock-down of PRAME

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PRAME induced inhibition of retinoic acid receptor signaling-mediated differentiation - a possible target for ATRA response in AML without t(15;17)

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Project description:Preferentially Expressed Antigen in Melanoma (PRAME) is frequently overexpressed in a wide variety of cancers and it has been proposed as prognostic marker for clinical outcome. It belongs to a class of non-mutated genes whose expression seems to be mostly restricted to tumor cells. Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Despite advances in the diagnosis and management of osteosarcoma, long-term survival has not envolved substantially in the past decades, justifying efforts in finding effective therapeutic targets. In order to assess transcriptome characteristics that could contribute to further comprehend PRAME association with cancer, the technique of gene expression profiling was used to compare PRAME-positive and PRAME-negative osteosarcoma samples. Keywords: disease state analysis Six tumor samples representing distinct histological classes of osteosarcoma (telangiectatic, giant cell, anaplastic, osteoblastic and chondroblastic) were included in this study. They were obtained from individual patients ranging from 5 to 29 years old. Microarray experiments were carried out using the microarray platform CodeLink (GE Healthcare). This platform utilizes bioarrays consisting of 30-base, single pre-validated oligonucleotide probe per gene target. CodeLink UniSet Human I bioarrays, containing 10,000 human transcripts, were used for all experiments. Hybridization procedures strictly followed protocols provided by the manufacturer (GE Healthcare). A total of 12 arrays were hybridized, including 6 tumor samples (3 PRAME-positive and 3 PRAME-negative) and their respective technical replicates. Arrays were scanned following the recommended scanning procedure and settings for use with CodeLink bioarrays (GE Healthcare) on GenePix 4000B Array Scanner/GenePix Pro 4.0 software (Axon Instruments).

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The tumor associated antigen PRAME exhibits dualistic functions that are targetable in diffuse large B cell lymphoma

Project description:PRAME is a prominent member of the cancer germline antigen family of proteins, which triggers autologous T-cell mediated immune responses. Integrative genomic analysis in diffuse large B-cell lymphoma (DLBCL) uncovered recurrent, and highly focal deletions of 22q11.22 including the PRAME gene, which were associated with poor outcome. PRAME-deleted tumors showed cytotoxic T-cell immune escape and were associated with cold tumor microenvironments. In addition, PRAME down-modulation was strongly associated with somatic EZH2 Y641 mutations in DLBCL, and PRC2-regulated genes were repressed in isogenic PRAME KO vs. PRAME wt lymphoma cell lines, with PRAME directly interacting with EZH2 as a negative regulator. EZH2 inhibition with EPZ-6438 abrogated these extrinsic and intrinsic effects leading to PRAME and microenvironment restoration in vivo. Our data highlight multiple functions of PRAME during lymphomagenesis, and provide a preclinical rationale for synergistic therapies combining epigenetic re-programming with PRAME-targeted therapies.

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| PRJNA1171866 | ENA

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