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Proteomic analysis of extracellular vesicles derived from Merkel cell carcinoma cell lines

ABSTRACT: Exosomes constitute an evolutionary conserved mechanism of intercellular signaling. Their importance are gaining increasing such as prognostic and diagnostic markers, and potential therapeutic tool. Merkel cell carcinoma (MCC) is an aggressive form of skin cancer with a poor prognosis. There are not available an effective systemic treatment for this type of cancer, and exosome-based therapy was proposed. We identified with high confident 164 exosome-derived proteins that were common for all four cell lines, which were annotated in ExoCarta and Vesiclepedia databases. This list includes proteins implicated in motility, metastasis and tumor progression.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Dr Ugo Moens

PROVIDER: MSV000080262 | MassIVE | Fri Oct 21 13:10:00 BST 2016

SECONDARY ACCESSION(S): PXD004198

REPOSITORIES: MassIVE

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Secretomic analysis of extracellular vesicles originating from polyomavirus-negative and polyomavirus-positive Merkel cell carcinoma cell lines.

Konstantinell Aelita A Bruun Jack-Ansgar JA Olsen Randi R Aspar Augusta A Škalko-Basnet Nataša N Sveinbjørnsson Baldur B Moens Ugo U

Proteomics 20160905 19

Extracellular vesicles or exosomes constitute an evolutionarily conserved mechanism of intercellular signaling. Exosomes are gaining an increasing amount of attention due to their role in pathologies, including malignancy, their importance as prognostic and diagnostic markers, and their potential as a therapeutic tool. Merkel cell carcinoma (MCC) is an aggressive form of skin cancer with a poor prognosis. Because an effective systemic treatment for this cancer type is currently not available, an ...[more]

PMID: 27402257

Similar Datasets

Proteomic analysis of extracellular vesicles derived from Merkel cell carcinoma cell lines

Project description:Exosomes constitute an evolutionary conserved mechanism of intercellular signaling. Their importance are gaining increasing such as prognostic and diagnostic markers, and potential therapeutic tool. Merkel cell carcinoma (MCC) is an aggressive form of skin cancer with a poor prognosis. There are not available an effective systemic treatment for this type of cancer, and exosome-based therapy was proposed. We identified with high confident 164 exosome-derived proteins that were common for all four cell lines, which were annotated in ExoCarta and Vesiclepedia databases. This list includes proteins implicated in motility, metastasis and tumor progression.

2016-08-08 | PXD004198 | Pride

Gene expression analysis of Merkel Cell Carcinoma

2010-12-15 | GSE22396 | GEO

Gene expression analysis of Merkel Cell Carcinoma

Project description:Merkel cell carcinoma (MCC) is a polyomavirus-associated skin cancer that is frequently lethal and lacks established prognostic biomarkers. The purpose of this study was to use gene expression analysis to identify biomarkers that may improve prognostic accuracy and provide insight into MCC biology. We profiled 35 tumors from 34 patients. Tumors were macrodissected from surrounding stroma. RNA isolation was performed with RNeasy or Allprep Mini kits (Qiagen, Alameda, CA), and RNA quality assessed by Agilent Bioanalyzer analysis. RNAs were profiled on the Human Rosetta Custom Affymetrix 2.0 chip.

2010-12-15 | E-GEOD-22396 | biostudies-arrayexpress

HR+/HER2- Breast Cancer Cell and Normal Breast Epithelial Cell Derived Exosome RNA Expression

Project description:AS a key medium for intercellular communication, exosome plays an important role in the occurrence and development of various forms of cancers, including breast cancer. However, the RNA from breast cancer-derived exosome remains to be explored. The HR+/HER2− breast cancer is the most common subgroup of breast cancer, we collected and primary cultured breast cancer and normal breast epithelial cells from three HR+/HER2− breast cancer patients, isolated the supernatant and extracted RNA from exosomes, and then performed microarray assays.

2023-10-01 | GSE207304 | GEO

Microarray analysis of Merkel cell carcinoma (MCC) tumors, small cell lung cancer (SCLC) tumors, and MCC cell lines

Project description:When using cell lines to study cancer, phenotypic similarity to the original tumor is paramount. Yet, little has been done to characterize how closely Merkel cell carcinoma (MCC) cell lines model native tumors. To determine their similarity to MCC tumor samples, we characterized MCC cell lines via gene expression microarrays. Using whole transcriptome gene expression signatures and a computational bioinformatic approach, we identified significant differences between variant cell lines (UISO, MCC13, and MCC26) and fresh frozen MCC tumors. Conversely, the classic WaGa and Mkl-1 cell lines more closely represented the global transcriptome of MCC tumors. When compared to publicly available cancer lines, WaGa and Mkl-1 cells were similar to other neuroendocrine tumors, but the variant cell lines were not. WaGa and Mkl-1 cells grown as xenografts in mice had histological and immunophenotypical features consistent with MCC, while UISO xenograft tumors were atypical for MCC. Spectral karyotyping and short tandem repeat analysis of the UISO cells matched the original cell line's description, ruling out contamination. Our results validate the use of transcriptome analysis to assess the cancer cell line representativeness and indicate that UISO, MCC13, and MCC26 cell lines are not representative of MCC tumors, whereas WaGa and Mkl-1 more closely model MCC. RNA was extracted from MCC cell lines and MCC and SCLC tumor samples and hybridized to Affymetrix microarrays for transcriptome profiling.

2014-12-23 | E-GEOD-50451 | biostudies-arrayexpress

Glucose-6-Phosphate Dehydrogenase as a Prognostic Predictor Correlates with the Tumor Immune Activity Including Programmed Death Ligand-1 Expression in Merkel Cell Carcinoma

Project description:Purpose: Merkel cell carcinoma (MCC) is a rare but highly malignant skin cancer. However, it is well known that some cases have a good prognosis including spontaneously regression. To precise such a different patient’s outcome, reported prognostic markers, e.g. Merkel cell polyoma virus infection or programmed death ligand-1 (PD-L1) expression, are still insufficient. Here we performed RNA sequencing to evaluate immune response and comprehensively estimate prognostic values of immunogenic factors in MCC.　 Experimental Design: We collected 90 specimens from 71 patients and 53 blood serum samples from 21 patients with MCC from 9 facilities. mRNA was extracted from formalin fixed paraffin embedded (FFPE) tissues. Analyses of next generation sequencing data, immunohistochemical staining and blood serum tests were performed. Results: Next generation sequencing revealed that MCC samples could be divided into two types. “immune active type” showed better clinical outcomes than “cell division type”. Glucose-6-Phosphate Dehydrogenase (G6PD) was one of the most significantly up-regulated gene in “cell division type”. G6PD expression correlated with the presence or absence of lymph node or distant metastases during the course and negatively correlated with high or low of PD-L1 expression with the top significance in 395 genes both. Immunohistochemical staining of G6PD was also correlated with disease specific survival and showed less heterogeneity compared with PD-L1 expression. G6PD activity was measurable by the blood serum test and detection values significantly increased as the cancer stage progression and significantly decreased after treatment. Conclusion: G6PD expression was an immunohistochemically and serum-detectable prognostic marker and negatively correlated with immune activity including PD-L1 associate with the prediction of immunotherapy response.

2020-12-13 | GSE154938 | GEO

Microarray analysis of Merkel cell carcinoma (MCC) tumors, small cell lung cancer (SCLC) tumors, and MCC cell lines

2014-12-23 | GSE50451 | GEO

LSD1 inhibition induces differentiation and cell death in Merkel cell carcinoma

Project description:Merkel cell carcinoma (MCC) is a highly aggressive, neuroendocrine skin cancer that lacks actionable mutations, which could be utilized for targeted therapies. Epigenetic regulators governing cell identity may represent unexplored therapeutic entry points. Here, we targeted epigenetic regulators in a pharmacological screen and discovered that the lysine-specific histone demethylase 1A (LSD1/KDM1A) is required for MCC growth in vitro and in vivo. We show that LSD1 inhibition in MCC disrupts the LSD1-CoREST complex leading to displacement and degradation of HMG20B (BRAF35), a poorly characterized complex member that is essential for MCC proliferation. Inhibition of LSD1 causes derepression of transcriptional master regulators of the neuronal lineage, activates a gene expression signature resembling normal Merkel cells, and induces cell cycle arrest and cell death. Our study unveils the importance of LSD1 for proliferation and maintaining cell identity in MCC. There is growing evidence that cancer cells exploit cellular plasticity and dedifferentiation programs to evade destruction by the immune system. The combination of LSD1 inhibitors with checkpoint inhibitors may thus represent a promising treatment strategy for MCC patients.

2020-11-03 | PXD020590 | Pride

GPR143 regulates ESCRT-dependent exosome biogenesis and promotes cancer metastasis

Project description:Exosomes transport a variety of macromolecules and modulate intercellular communication in physiology and disease. However, the regulation mechanisms that determine exosome contents during exosome biogenesis remain poorly understood. Here, we identify GPR143, an atypical GPCR, as a regulator of the endosomal sorting complex required for transport (ESCRT)-dependent exosome biogenesis pathway. GPR143 interacts with HRS (an ESCRT-0 Subunit) and promotes its association to cargo proteins, such as EGFR, which subsequently enables selective protein sorting into intralumenal vesicles (ILVs) in multivesicular bodies (MVBs). GPR143 is elevated in multiple cancers and quantitative proteomic and RNA profiling of exosomes revealed the GPR143-ESCRT pathway promotes secretion of exosomes that carry unique cargo, including integrins signaling proteins. By gain- and loss-of-function studies, we reveal GPR143 promotes metastasis by secreting exosomes and increasing cell motility/invasion through the integrin/FAK/Src pathway. These finding uncover a mechanism that regulates the exosomal proteome and demonstrate its ability to promote cancer metastasis.

2022-12-20 | PXD031515 | Pride

Impact of increased core fucosylation on the exosome proteome in prostate cancer

Project description:Prostate cancer is the most commonly diagnosed oncogenic malignancy in men worldwide, resulting in almost 30,000 cancer-related deaths in the United States each year. Wider examination of aberrant glycosylation in prostate cancer has revealed increased expression of the glycotransferase involved in core fucosylation, (1,6)fucosyltranferase (FUT8) associating with aggressive (AG) prostate cancer and castration-resistance, with functional analyses revealing FUT8 impacting cell motility and invasiveness in prostate cancer cells. Exosomes are extracellular microvesicles (30-150 nm) that are involved in in both proximal and distal intercellular communication via the transport of proteins and nucleic acids (mRNA, miRNA, and DNA). To gain insight into the impact of increased cellular FUT8 expression on exosome biogenesis and protein cargo profiles in prostate cancer, we paired Nanoparticle Tracking Analysis (NTA) and stable isotope labelling with amino acids in cell culture (SILAC) quantitative proteomics.

2020-05-13 | PXD013340 | Pride

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