Dataset Information

Quantitative proteomic analysis reveals effects of EGFR on invasion-promoting proteins secreted by glioblastoma cells.

ABSTRACT: Data from PeptideAtlas, [[http://www.peptideatlas.org/PASS/PASS00455 PASS00455]]. Experiment: PTEN+EGFR_1, file: folder summary. Published as part of Mol Cell Proteomics. 2014 Jul 5 . From the Abstract: {{i}} ... To better understand how EGFR contributes to tumor aggressiveness, we investigated the effect of EGFR on the secreted levels of 65 rationally selected proteins involved in invasion. We employed selected reaction monitoring (SRM) targeted mass spectrometry using stable isotope labeled internal peptide standards to quantity proteins in the secretome from five GBM (U87) isogenic cell lines in which EGFR, EGFRvIII and/or PTEN were expressed. {{/i}}

INSTRUMENT(S): Instrument

ORGANISM(S): Homo_sapiens_viruses, Human

DISEASE(S): Not Available

SUBMITTER: Vineet Sangar, et al.

PROVIDER: GPM11210028781 | GPMDB |

REPOSITORIES: GPMDB

ACCESS DATA

Publications

Quantitative proteomic analysis reveals effects of epidermal growth factor receptor (EGFR) on invasion-promoting proteins secreted by glioblastoma cells.

Sangar Vineet V Funk Cory C CC Kusebauch Ulrike U Campbell David S DS Moritz Robert L RL Price Nathan D ND

Molecular & cellular proteomics : MCP 20140705 10

Glioblastoma multiforme is a highly invasive and aggressive brain tumor with an invariably poor prognosis. The overexpression of epidermal growth factor receptor (EGFR) is a primary influencer of invasion and proliferation in tumor cells and the constitutively active EGFRvIII mutant, found in 30-65% of Glioblastoma multiforme, confers more aggressive invasion. To better understand how EGFR contributes to tumor aggressiveness, we investigated the effect of EGFR on the secreted levels of 65 ration ...[more]

PMID: 24997998

Similar Datasets

Project description:Co-infections of Candida albicans and Staphylococcus aureus can significantly increase morbidity and mortality. This synergism is linked to the interactions between C. albicans and S. aureus that allow for staphylococcal co-invasion and dissemination. While it is known that virulence factors contribute to this process, the effect of C. albicans-S. aureus coculturing on virulence factors composition and macrophage-mediated inflammation remain unknown. In this study, we used mass spectrometry-proteomics to investigate the effect of coculturing on the composition of the >3 kDa protein fraction of the S. aureus and C. albicans secretome, as well as the secretomal cytotoxicity and proinflammatory effects on human oral cells and immune cells. Results showed that coculturing of C. albicans and S. aureus promoted the secretion of 7 cytolytic, 11 proteolytic, and 3 lipolytic extracellular virulence factors (ECVFs). While the majority of differentially released C. albicans ECVFs were attributable to Als1/Als3-mediated interactions, changes in S. aureus secretomal ECVF composition were mainly attributable to the presence of C. albicans or its pH maintenance. By analysing both secreted and non-secreted virulence factors, it appears that coculturing promotes C. albicans hypha formation together with β-glucan masking, suggesting that coculturing enhances both C. albicans invasion and immune evasion. In addition, coculturing increased the cytotoxic potential of the secretome towards human oral epithelial cells and macrophages compared to the summed cytotoxic effect of both monoculture secretomes. Under non-cytotoxic conditions, the secretome of C. albicans-S. aureus coculture promoted macrophage activation and increased gene transcription of pro-inflammatory pathways compared to monoculture secretomes. Surprisingly, ALS1/ALS3 knock out has marginal effects on the secretome-increased proinflammation in macrophages. Our findings support that C. albicans and S. aureus reciprocally promotes their virulence potential, cytotoxicity, and proinflammatory effects, which may provide insights into the synergistic lethality during their coinfection in vivo.

Project description:Background: Advanced Renal cell carcinoma (RCC) is therapeutically challenging. RCC progression is facilitated by mesenchymal stem/stromal cells (MSCs) that exert remarkable tumor tropism. The specific mechanisms mediating MSCs’ migration to RCC remain unknown. Here, we comprehensively analyzed RCC secretome to identify MSCs attractants. Methods: Conditioned media (CM) were collected from five RCC-derived cell lines (Caki-1, 786-O, A498, KIJ265T, KIJ308T) and non-tumorous control cell line (RPTEC/TERT1) and analyzed using cytokine arrays targeting 274 cytokines in addition to global CM proteomics. MSCs were isolated from bone marrow of patients undergoing standard orthopedic surgeries. RCC CM and the selected recombinant cytokines were used to analyze their influence on MSCs migration and microarray-targeted gene expression. The expression of genes encoding cytokines was evaluated in 100 matched-paired control-RCC tumor samples. Results: When compared with normal cells, CM from advanced RCC cell lines (Caki-1, KIJ265T) were the strongest stimulators of MSCs migration. Targeted analysis of 274 cytokines and global proteomics of RCC CM revealed decreased DPP4 and EGF, as well as increased AREG, FN1, and MMP1, with consistently altered gene expression in RCC cell lines and tumors. AREG and FN1 stimulated, while DPP4 attenuated MSCs migration. RCC CM induced MSCs’ transcriptional reprogramming, stimulating the expression of CD44, PTX3, and RAB27B. RCC cells secreted hyaluronic acid (HA), a CD44 ligand mediating MSCs’ homing to the kidney. AREG emerged as an upregulator of MSCs’ transcription. Conclusions: advanced RCC cells secrete AREG, FN1 and HA to induce MSCs migration, while DPP4 loss prevents its inhibitory effect on MSCs homing. RCC secretome induces MSCs’ transcriptional reprograming to facilitate their migration. The identified components of RCC secretome represent potential therapeutic targets. We used microarrays to determine the effect of the conditioned media (CM) collected from two RCC-derived cell lines (Caki-1, KIJ265T) and non-tumorous control cell line (RPTEC/TERT1) on the transcriptome change in mesenchymal stem/stromal cells (MSCs).

Dataset Information

Quantitative proteomic analysis reveals effects of EGFR on invasion-promoting proteins secreted by glioblastoma cells.

Publications

Quantitative proteomic analysis reveals effects of epidermal growth factor receptor (EGFR) on invasion-promoting proteins secreted by glioblastoma cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets