Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Interfering with aggregated α-synuclein in advanced melanoma leads to a major upregulation of MHC class II proteins

ABSTRACT: Melanoma is the most serious and deadly form of skin cancer and with progression to advanced melanoma, the intrinsically disordered protein α-synuclein is upregulated to high levels; and while toxic to dopaminergic neurons in Parkinson’s disease, it is highly beneficial for primary and metastatic melanoma cells. To gain detailed insights, both at the level of the proteome and the transcriptome, into this exact opposite role of α-synuclein in advanced melanoma, we performed proteome and transcriptome studies of high-level α-synuclein-expressing primary and metastatic human melanoma cell lines and metastatic human melanoma xenografts treated with the small-molecule diphenyl-pyrazole compound anle138b, which binds to and interferes with the oligomeric structure of α-synuclein. Our data demonstrate that interfering with oligomerized α-synuclein in these melanoma cells and tumor xenografts leads to a substantial upregulation of major histocompatibility complex (MHC) proteins, which are important for enhancing anti-melanoma immune responses.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Melanocyte, Cell Culture, Melanoma Cell Line

DISEASE(S): Melanoma

SUBMITTER: Ivan Silbern

LAB HEAD: Prof. Dr. Henning Urlaub

PROVIDER: PXD030615 | Pride | 2024-07-03

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20180621_uniprot_homo_canonical.fasta	Fasta
	20180621_uniprot_homo_mus_canonical.fasta	Fasta
	D_Becker_160517_040717_TMT_Mix1-6_TMTSPS.raw	Raw
	D_Becker_160517_040717_TMT_Mix1-6_TMTSPS_rep1.raw	Raw
	D_Becker_160517_040717_TMT_Mix1-6_TMTSPS_rep2.raw	Raw

Items per page:

1 - 5 of 258

Similar Datasets

Interfering with aggregated α-synuclein in advanced melanoma leads to a major upregulation of MHC class II proteins

Project description:Melanoma is the most serious and deadly form of skin cancer and with progression to advanced melanoma, the intrinsically disordered protein α-synuclein is upregulated to high levels; and while toxic to dopaminergic neurons in Parkinson’s disease, it is highly beneficial for primary and metastatic melanoma cells. To gain detailed insights, both at the level of the proteome and the transcriptome, into this exact opposite role of α-synuclein in advanced melanoma, we performed proteomic studies of high-level α-synuclein-expressing primary and metastatic human melanoma cell lines and proteomic and transcriptomic studies of metastatic human melanoma xenografts treated systemically with the diphenyl-pyrazole small-molecule compound anle138b, which binds to and interferes with the oligomeric structure of α-synuclein. The results of these studies reveal that interfering with oligomerized α-synuclein in these tumor xenografts led to a substantial upregulation of expression of major histocompatibility complex proteins in the melanoma cells, the latter of which is pertinent to enhancing anti-melanoma immune responses.

2024-05-21 | GSE240854 | GEO

Dissection of cancer cell and stromal cell-derived signals in melanoma xenografts following treatment with the stromal-targeting agent DMXAA

Project description:5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a tumor vascular disrupting agent, is shown here to have substantial activity as a single agent against human A375 melanoma xenografts in nude mice (94 % hemorrhagic necrosis after 24 h, and 26 days growth delay following single dose at 25 mg/kg). CD45+ cells in tumor tissue increased 5-fold over the first 3 days after treatment, which was due largely to an influx of CD11b+ Ly6G+ neutrophils. Using murine and human multiplex cytokine assays to dissect the cytokines produced by host stromal cells or by the melanoma cells, it was shown that both the stromal cells and the A375 melanoma cells produced cytokines capable of attracting neutrophils into the tumor. The same xenografts were also analyzed using human and mouse Affymetrix microarrays to separately identify tumor cell-specific (human) and stromal cell-specific (mouse) gene expression changes. DMXAA induced numerous stromal cytokine mRNAs, including IP-10, IL-6, MIP-1α/β, MIP-2, KC, RANTES, MIG, MCP-1 and IL-1β, many of which were also elevated at the protein level. Numerous human cytokine mRNAs were also induced including MCP-1, IL-8, GRO, VEGF, GM-CSF and IL-6, which again was in line with our protein data. Pathway analysis indicated that significant numbers of the stromal mRNAs induced by DMXAA are regulated downstream of TNF-α, interferon-β and NFκB. Our results suggest that DMXAA may have utility in combination therapy for human melanoma through the activation of pro-inflammatory signalling pathways and cytokine expression from both stromal and tumor cells, leading to haemorrhagic necrosis, neutrophil influx and growth inhibition. Microarrays were used to identify separately the abundance of tumour cell and stromal cell RNA in A375 melanoma xenografts, with and without treatment by the stromal targetting drug DMXAA.

2012-03-15 | E-GEOD-26308 | biostudies-arrayexpress

B16 versus B16B1

Project description:Analysis of gene expression patterns in cancer improved the understanding the mechanisms underlying the process of metastatic progression. Recent studies have attributed an important role to B-1 cells, a subset of B lymphocytes, in melanoma progression. It was already demonstrated that in vitro interaction between B16 melanoma cells and B-1 lymphocytes induced increase in metastatic potential of B16 lineage. In this study we used a microarray approach to assess gene expression profile in B16 melanoma cells after contacting B-1 lymphocytes (B16B1).

2013-06-05 | E-MEXP-3599 | biostudies-arrayexpress

Type-1-cytokines synergize with oncogene inhibition to induce tumor growth arrest

Project description:Both targeted inhibition of oncogenic driver mutations and immune-based therapies show efficacy in treatment of patients with metastatic cancer but responses are either short-lived or incompletely effective. Oncogene inhibition can augment the efficacy of immune-based therapy but mechanisms by which these two interventions might cooperate are incompletely resolved. Using a novel transplantable BRAFV600E-mutant murine melanoma model (SB-3123), we explore potential mechanisms of synergy between the selective BRAFV600E inhibitor vemurafenib and adoptive cell transfer (ACT)-based immunotherapy. We found that vemurafenib cooperated with ACT to delay melanoma progression but surprisingly did not enhance tumor infiltration or effector function of endogenous or adoptively transferred CD8+ T cells as previously observed. Instead, we found that the T cell cytokines IFN-gamma and TNF-alpha synergized with vemurafenib to induce cell cycle arrest of tumor cells in vitro. This was recapitulated in vivo as continuous vemurafenib administration was required to delay melanoma progression following ACT. The unexpected finding that immune cytokines synergize with oncogene inhibitors to induce growth arrest have major implications for understanding cancer biology at the intersection of oncogenic and immune signaling and provides a basis for design of combinatorial therapeutic approaches for patients with metastatic cancer. SB-3123p cells were treated in triplicate (biological replicates) under the following conditions for 96 hours: DMSO vehicle (control) (n=3); mouse IFNgamma (2.4 ng/ml) and mouse TNFalpha (0.24 ng/mL) (n=3); Vemurafenib (1uM) (n=3); and mouse IFNgamma (2.4 ng/ml), mouse TNFalpah (0.24 ng/mL) and Vemurafenib (1uM) (n=3).

2015-02-20 | E-GEOD-62249 | biostudies-arrayexpress

Transcriptional response to TNF-alpha in a panel of 17 human melanoma cell lines

Project description:A panel of 17 human melanoma cell lines with known BRAF and NRAS mutation status was stimulated with TNF-alpha for 72 hours. The goal of the study was to correlate the transcriptional response in BRAF versus NRAS mutated melanoma cell lines. Total RNA was obtained from a panel of 17 human melanoma cell lines treated for 72 hours with TNF-alpha or left untreated. Gene expression profiling was done using the Illumina Human HT12 v4 platform.

2014-02-10 | E-GEOD-51221 | biostudies-arrayexpress

Analysis of p53 target genes in melanoma part 1

Project description:Although mutations in p53 are infrequent in human melanoma, its function is abnormal. In this study, whole genome bead arrays were used to examine the expression of p53 target genes in extracts from 82 metastatic melanoma samples, compared to extracts derived from diploid human melanocytes, to provide a global assessment of aberrant p53 function. Total RNA extracted from 82 tumour samples and 8 melanocyte cell lines was analysed. Metastatic melanomas were compared to melanocyte cell lines.

2011-12-01 | E-GEOD-29359 | biostudies-arrayexpress

Genome-wide promoter methylation analysis associated with malignant melanoma progression

Project description:Epigenetic alterations play significant roles in the melanoma tumorigenesis and malignant progression. We profiled genome-wide promoter DNA methylation patterns of melanoma cells deribed from primary lesions of Radial Growrth phase (RGP) and Vertical Growth Phase (VGP), metastatic lesions, and primary normal melanocytes by interrogating 14,495 genes using Illumina bead chip technology. By comparative analysis of the promoter methylation profiles, we identified epigenetically silenced gene signatures that potentially associated with malignant melanoma progression. Bisulphite converted genomic DNA from a group of melanoma cells representing pathologic stages of melanoma progression (3 cell lines derived from RGP melanoma lesions, 4 cell lines derived from VGP lesions, and 3 melastatic melanomas) and normal human primary melanocytes isolated from lightly pigmented adult skin were hybridized to Illumina's Infinium HumanMethylation27 BeadChips

2013-12-20 | E-GEOD-53516 | biostudies-arrayexpress

Modulation of the transcriptional response to TNF-alpha in the human melanoma cell line MZ7 by MITF

Project description:We analyzed the transcriptional response of the human melanoma cell line MZ7 to TNF-alpha (24 hours) in a dose-dependent manner (TNF-alpha 10U/ml, 100U/ml, 1000U/ml) either transfected with control siRNA (siNT = non-targeting siRNA) or transfected with siRNAs (pool of 4 active and independent siRNAs) against the melanocytic transcription factor and lineage oncogene MITF. (Microphthalmia-associated transcription factor). The experiment was performed as biological duplicate. As MITF is critical for melanoma cell state control, we aimed to explore how MITF expression intersects with inflammation-induced plasticity pathways in melanoma. Total RNA was obtained from siRNA/TNF-treated MZ7 melanoma cell lines at various conditions and global gene expression profiling was done using the Illumina Human HT12 v4 platform.

2015-10-29 | E-GEOD-71798 | biostudies-arrayexpress

Propranolol inhibition of melanoma growth

Project description:We investigated the effect of a daily propranolol treatment (0.5mg/mL in the water bottle) on human melanoma xenografts development and the subsequent transcriptomic variations

2014-05-30 | E-MTAB-2404 | biostudies-arrayexpress

Propranolol inhibition of melanoma growth

2014-05-30 | E-MTAB-2405 | biostudies-arrayexpress