Discovery of putative pancreatic cancer biomarkers using subcellular proteomics

McKinney, Kimberly Q.; Lee, Yong-Yook; Choi, Hyun-Su; Groseclose, Gale; Iannitti, David A.; Martinie, John B.; Russo, Mark W.; Lundgren, Deborah H.; Han, David K.; Bonkovsky, Herbert L.; Hwang, Sun-Il

doi:10.1016/j.jprot.2010.08.006

Cited by 29 publications

(23 citation statements)

References 46 publications

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“…Both the method of sample preparation and the sensitivity of the mass spectrometer influence the number of proteins identified. In a recent study evaluating pancreatic cancer biomarkers by crude cell fractionation, 1D gel electrophoresis and HPLC of 20 gel slices, over 2000 proteins were identified (37). However, since most cell types are estimated to contain around 5000 proteins and the pancreas contains multiple cell types, it is clear that not all low abundance proteins are yet being identified.…”

Section: Conclusion and Recommendations For Future Proteomic Studiesmentioning

confidence: 99%

Proteomics as a Systems Approach to Pancreatitis

Williams¹

2013

Pancreas

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Proteomics is an approach to looking at the identity, amount, proteolysis, compartmentalization and post-translational modification of a large number of proteins simultaneously in a cell or tissue. Recently, proteomics has begun to be applied to the study of pancreatitis to ascertain mechanisms of disease and search for biomarkers of disease. Most mechanistic work has been carried out in animal models of acute pancreatitis. In eight studies, 97 proteins have been reported to increase, 55 to decrease and 23 to undergo proteolysis. Proteins showing increases are most often related to stress, inflammation or the cytoskeleton while decreases are seen in digestive enzymes and proteins related to metabolism. Many protein changes however, are not consistent between studies and only the most recent studies are rigorous and quantitative. By contrast, biomarker studies have focused on pancreatic juice and plasma of humans with disease and often are directed at distinguishing chronic pancreatitis from cancer. Chronic pancreatitis has also been investigated in tissue sections of histological samples. In this review the results of studies to date are described as well as coverage of the methods used and special issues that must be considered. Areas are pointed out that are worthy of future study.

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Section: Conclusion and Recommendations For Future Proteomic Studiesmentioning

confidence: 99%

Proteomics as a Systems Approach to Pancreatitis

Williams¹

2013

Pancreas

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“…6 Our laboratory and others have reported the overexpression of myoferlin in several cancers including pancreatic adenocarcinoma at both gene [7][8][9] and protein levels. [10][11][12] However, very few studies have yet explored the potential role of this protein in cancer progression and development. Recently, myoferlin was found to be important for breast cancer invasion.…”

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confidence: 99%

Myoferlin plays a key role in VEGFA secretion and impacts tumor‐associated angiogenesis in human pancreas cancer

Fahmy

Gonzalez

Arafa

et al. 2015

Intl Journal of Cancer

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Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas adenocarcinoma where its expression was associated to a bad prognosis. However, the function of myoferlin in pancreas adenocarcinoma has not been reported. In other cell types, myoferlin is involved in several key plasma membrane processes such as fusion, repair, endocytosis and tyrosine kinase receptor activity. In this study, we showed that myoferlin silencing in BxPC-3 human pancreatic cancer cells resulted in the inhibition of cell proliferation in vitro and in a significant reduction of the tumor volume in chick chorioallantoic membrane assay. In addition to be smaller, the tumors formed by the myoferlin-silenced cells showed a marked absence of functional blood vessels. We further demonstrated that this effect was due, at least in part, to an inhibition of VEGFA secretion by BxPC-3 myoferlin-silenced cells. Using immunofluorescence and electron microscopy, we linked the decreased VEGFA secretion to an impairment of VEGFA exocytosis. The clinical relevance of our results was further strengthened by a significant correlation between myoferlin expression in a series of human pancreatic malignant lesions and their angiogenic status evaluated by the determination of the blood vessel density.

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“…The splenic marginated pool of immune cells is in dynamic equilibrium with the circulating immune cells, and includes 10 -15% of the body's B lymphocytes (20,21), 25% of the body's T lymphocytes (20,21), 21-34% of the body's granulocytes (22,23), and 50% of the body's monocytes (24) (this reserve of monocytes can exit the spleen and differentiate to become dendritic cells and macrophages). The strategy of using comparative proteomics to study altered tissues to generate lists of candidate biomarkers has been employed previously, primarily because of the difficulty of discovering biomarkers directly from the blood (25)(26)(27)(28)(29)(30)(31)(32). Host response signaling events within mouse spleens may translate into presymptomatic diagnostic biomarkers of human anthrax detectable within circulating immune cells, and could aid in the identification of pathogenic mechanisms and therapeutic targets.…”

mentioning

confidence: 99%

Discovery of Mouse Spleen Signaling Responses to Anthrax using Label-Free Quantitative Phosphoproteomics via Mass Spectrometry

Manes

Dong

Zhou

et al. 2011

Molecular & Cellular Proteomics

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Inhalational anthrax is caused by spores of the bacteriumBacillus anthracis (B. anthracis), and is an extremely dangerous disease that can kill unvaccinated victims within 2 weeks. Modern antibiotic-based therapy can increase the survival rate to ϳ50%, but only if administered presymptomatically (within 24 -48 h of exposure). To discover host signaling responses to presymptomatic anthrax, labelfree quantitative phosphoproteomics via liquid chromatography coupled to mass spectrometry was used to compare spleens from uninfected and spore-challenged mice over a 72 h time-course. Spleen proteins were denatured using urea, reduced using dithiothreitol, alkylated using iodoacetamide, and digested into peptides using trypsin, and the resulting phosphopeptides were enriched using titanium dioxide solid-phase extraction and analyzed by nano-liquid chromatography-Linear Trap Quadrupole-Orbitrap-MS(/MS). The fragment ion spectra were processed using DeconMSn and searched using both Mascot and SEQUEST resulting in 252,626 confident identifications of 6248 phosphopeptides (corresponding to 5782 phosphorylation sites). The precursor ion spectra were deisotoped using Decon2LS and aligned using MultiAlign resulting in the confident quantitation of 3265 of the identified phosphopeptides. ANOVAs were used to produce a q-value ranked list of host signaling responses. Late-stage (48 -72 h postchallenge) Sterne strain (lethal) infections resulted in global alterations to the spleen phosphoproteome. In contrast, ⌬Sterne strain (asymptomatic; missing the anthrax toxin) infections resulted in 188 (5.8%) significantly altered (q<0.05) phosphopeptides. Twenty-six highly tentative phosphorylation responses to early-stage (24 h postchallenge) anthrax were discovered (q<0.5), and ten of these originated from eight proteins that have known roles in the host immune response. These tentative early-anthrax host response signaling events within mouse spleens may translate into presymptomatic diagnostic biomarkers of human anthrax detectable within circulating immune cells, and could aid in the identification of pathogenic mechanisms and therapeutic targets.

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Discovery of putative pancreatic cancer biomarkers using subcellular proteomics

Cited by 29 publications

References 46 publications

Proteomics as a Systems Approach to Pancreatitis

Proteomics as a Systems Approach to Pancreatitis

Myoferlin plays a key role in VEGFA secretion and impacts tumor‐associated angiogenesis in human pancreas cancer

Discovery of Mouse Spleen Signaling Responses to Anthrax using Label-Free Quantitative Phosphoproteomics via Mass Spectrometry

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