Glioblastoma cell secretome: Analysis of three glioblastoma cell lines reveal 148 non-redundant proteins

Polisetty, Ravindra Varma; Gupta, Manoj Kumar; Nair, Sudha C.; Ramamoorthy, Kalidoss; Tiwary, Shivani; Shiras, Anjali; Chandak, Giriraj Ratan; Sirdeshmukh, Ravi

doi:10.1016/j.jprot.2011.05.002

Cited by 34 publications

(33 citation statements)

References 32 publications

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“…To filter out likely intracellular contaminants and retain proteins most likely to be secreted by live cells, we used the SignalP [26,27] and Gene Ontology (GO) [28,29] databases to retain only proteins either experimentally observed to be extracellular or otherwise containing predicted cleavable signal peptides targeting them to the secretory pathway. This analysis yielded a total of 298 unique, secretory-predicted proteins across the eight cell lines, which is in line with previous quantities and percentages of secreted proteins found in comparable secretome analyses [8,[30][31][32][33][34][35][36][37][38][39][40].…”

Section: Non-quantitative Bone Metastasis Secretome Analysissupporting

confidence: 84%

“…The first breast cancer metastasis secretome study profiled the secretomes of the MCF10A metastasis progression series, finding proteins such as alpha-1-antichymotrypsin and galectin-3-binding protein to be upregulated in conditioned media from the metastatic variants [48]. More recently, many secretome analyses of cell lines representing several different cancer types have been reported [8,[30][31][32][33][34][35][36][37][38][39][40]. Most secretome studies have used methodology similar to ours in terms of initial protein harvesting conditions and then have typically used either concentrating columns or total protein precipitation methods for secreted protein isolation.…”

Section: Mario Andres Blanco Et Al 1349mentioning

confidence: 99%

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Global secretome analysis identifies novel mediators of bone metastasis

et al. 2012

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Bone is the one of the most common sites of distant metastasis of solid tumors. Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma. To comprehensively profile secreted proteins associated with bone metastasis, we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types. By comparing the secretomes of parental cells and their bone metastatic derivatives, we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines. We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis. Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1, CST2, and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1. Overall, our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

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Section: Non-quantitative Bone Metastasis Secretome Analysissupporting

confidence: 84%

Section: Mario Andres Blanco Et Al 1349mentioning

confidence: 99%

Global secretome analysis identifies novel mediators of bone metastasis

et al. 2012

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“…2), the number of unique secreted proteins was in the range of ϳ300 -450/replicate. Previous studies by Polisetty et al (58) and Formola et al (59) also reported a relatively modest number (Ͻ150) of secreted proteins from the U87MG cell line when they compared multiple GBM cell lines. The secretome of GBM cells contained pro- teins implicated in a wide range of functions, with the most prominent functions including wounding, cell death, apoptosis, cytoskeleton organization, cell adhesion, cell motion, angiogenesis, and adherens junction (supplemental Table S1).…”

Section: Discovery Proteomics Reveals Predominance Of Invasionpromotimentioning

confidence: 95%

“…Interestingly, CHI3L1 (Chitinase 3-like 1), a secreted glycoprotein, which has been implicated in invasion and cell matrix adhesion (62), was observed at higher levels in the secretome of U87 cells (58,59) and was present at lower levels in the EGFR-and EGFRvIII-expressing cell lines compared with U87 parental, ϩPE-and ϩPTEN-expressing cells. For the ϩPE cell line, 32 proteins were detected and CTSL1 protein; an endopeptidase inhibitor was present at the highest level.…”

Section: Pten-and Pe-expressing Cell Lines Had Low Abundance Of Invasmentioning

confidence: 99%

Quantitative Proteomic Analysis Reveals Effects of Epidermal Growth Factor Receptor (EGFR) on Invasion-promoting Proteins Secreted by Glioblastoma Cells

Sangar

Funk

Kusebauch

et al. 2014

Molecular & Cellular Proteomics

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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 rationally selected proteins involved in invasion. We employed selected reaction monitoring 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. Our results show that cell lines with EGFR overexpression and constitutive EGFRvIII expression differ remarkably in the expression profiles for both secreted and intracellular signaling proteins, and alterations in EGFR signaling result in reproducible changes in concentrations of secreted proteins. Furthermore, the EGFRvIII-expressing mutant cell line secretes the majority of the selected invasion-promoting proteins at higher levels than other cell lines tested. Additionally, the intracellular and extracellular protein measurements indicate elevated oxidative stress in the EGFRvIIIexpressing cell line. In conclusion, the results of our study demonstrate that EGFR signaling has a significant effect on the levels of secreted invasion-promoting proteins, likely contributing to the aggressiveness of Glioblastoma multiforme. Further characterization of these proteins may provide candidates for new therapeutic strategies and targets as well as biomarkers for this aggressive disease. Molecular & Cellular

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“…Secretome proteins play a key role in cell signaling, communication and migration [20]. The current protein-based serum biomarkers in lung cancer clinical practice include carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1), tissue polypeptide antigen (TPA), pro-gastrin releasing peptide (ProGRP), neuron-specific enolase (NSE) and tumor M2 pyruvate kinase [21].…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

Liquid biopsies in lung cancer: The new ambrosia of researchers

Rolfo

Castiglia

Hong

et al. 2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

134

124

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In the last decades the approach to cancer patient management has been deeply revolutionized. We are moving from a "one-fits-all" strategy to the "personalized medicine" based on the molecular characterization of the tumor. In this new era it is becoming more and more clear that the monitoring of the disease is fundamental for the success of the treatment, thus there is the need of new biomarker discovery. More precisely in the last years the scientific community has started to use the term "liquid biopsy". A liquid biopsy is a liquid biomarker that can be easily isolated from many body fluids (blood, saliva, urine, ascites, pleural effusion, etc.) and, as well as a tissue biopsy, a representative of the tissue from which it is spread. In this review we will focus our attention on circulating tumor cells, circulating tumor DNA, exosomes and secretomes with the aim to underlie their usefulness and potential application in a clinical setting for lung cancer patient management.

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Glioblastoma cell secretome: Analysis of three glioblastoma cell lines reveal 148 non-redundant proteins

Cited by 34 publications

References 32 publications

Global secretome analysis identifies novel mediators of bone metastasis

Global secretome analysis identifies novel mediators of bone metastasis

Quantitative Proteomic Analysis Reveals Effects of Epidermal Growth Factor Receptor (EGFR) on Invasion-promoting Proteins Secreted by Glioblastoma Cells

Liquid biopsies in lung cancer: The new ambrosia of researchers

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