Abstract：
:Hypoxia is present in most solid tumors and is clinically correlated with increased metastasis and poor patient survival. While studies have demonstrated the role of hypoxia and hypoxia-regulated proteins in cancer progression, no attempts have been made to identify hypoxia-regulated proteins using quantitative proteomics combined with MALDI-mass spectrometry imaging (MALDI-MSI). Here we present a comprehensive hypoxic proteome study and are the first to investigate changes in situ using tumor samples. In vitro quantitative mass spectrometry analysis of the hypoxic proteome was performed on breast cancer cells using stable isotope labeling with amino acids in cell culture (SILAC). MS analyses were performed on laser-capture microdissected samples isolated from normoxic and hypoxic regions from tumors derived from the same cells used in vitro. MALDI-MSI was used in combination to investigate hypoxia-regulated protein localization within tumor sections. Here we identified more than 100 proteins, both novel and previously reported, that were associated with hypoxia. Several proteins were localized in hypoxic regions, as identified by MALDI-MSI. Visualization and data extrapolation methods for the in vitro SILAC data were also developed, and computational mapping of MALDI-MSI data to IHC results was applied for data validation. The results and limitations of the methodologies described are discussed.
journal_name
J Proteome Resjournal_title
Journal of proteome researchauthors
Djidja MC,Chang J,Hadjiprocopis A,Schmich F,Sinclair J,Mršnik M,Schoof EM,Barker HE,Linding R,Jørgensen C,Erler JTdoi
10.1021/pr401056csubject
Has Abstractpub_date
2014-05-02 00:00:00pages
2297-313issue
5eissn
1535-3893issn
1535-3907journal_volume
13pub_type
杂志文章abstract：:HER2-testing in breast and gastric cancers is mandatory for the treatment with trastuzumab. We hypothesized that imaging mass spectrometry (IMS) of breast cancers may be useful for generating a classifier that may determine HER2-status in other cancer entities irrespective of primary tumor site. A total of 107 breast ...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr100573s
更新日期：2010-12-03 00:00:00
abstract：:Protein post-translational modification by ubiquitin-fold modifier 1, UFM1, regulates many biological processes such as response to endoplasmic reticulum stress and regulation of tumor progression. A recent study has indicated that the UFM1-binding and PCI domain-containing protein 1 (UFBP1) is required for the conjug...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.7b00843
更新日期：2018-04-06 00:00:00
abstract：:The protein kinase AKT is a central kinase in the heart and has a major impact on growth/hypertrophy, survival/apoptosis, and metabolism. To gain more insight into AKT isoform-specific signaling at the molecular level, we investigated the phosphoproteome of HL-1 cardiomyocytes carrying AKT1 or AKT2 isoform-specific kn...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr500131g
更新日期：2014-10-03 00:00:00
abstract：:Cyanobacteria developed efficient carbon concentrating mechanisms which significantly improve the photosynthetic performance and survival of cells under limiting CO(2) conditions. Dynamic changes of the Synechocystis proteome to CO(2) limitation were investigated using shotgun LC-MS/MS approach with isobaric tag for r...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr100651w
更新日期：2010-11-05 00:00:00
abstract：:Hepatocellular carcinoma (HCC) causes more than half a million annual deaths worldwide. Understanding the mechanisms contributing to HCC development is highly desirable for improved surveillance, diagnosis, and treatment. Liver tissue metabolomics has the potential to reflect the physiological changes behind HCC devel...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.9b00185
更新日期：2019-08-02 00:00:00
abstract：:Although tandem mass spectrometry (MS/MS) has become an integral part of proteomics, intensity patterns in MS/MS spectra are rarely weighted heavily in most widely used algorithms because they are not yet fully understood. Here a knowledge mining approach is demonstrated to discover fragmentation intensity patterns an...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr070106u
更新日期：2008-01-01 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.8b00012
更新日期：2018-07-06 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr100406z
更新日期：2010-09-03 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr060152e
更新日期：2006-09-01 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr200088w
更新日期：2011-06-03 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr050133p
更新日期：2005-11-01 00:00:00
abstract：:Proteomic studies were performed to identify the protein species involved in copper (Cu) stress responses in common wheat. Two-week-old wheat seedlings were exposed to 100 μM CuSO4 treatment for 3 days. Growth of shoots and roots was markedly inhibited and lipid peroxidation was greatly increased. Cu was readily absor...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr4008283
更新日期：2013-11-01 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr300953k
更新日期：2013-02-01 00:00:00
abstract：:The process of extracting comprehensive proteome representations is a crucial step for many proteomic studies. While antibody microarrays are an evolving and promising methodology in proteomics, the issue of protein extraction from tissues for this kind of analysis has never been addressed. Here, we describe a single-...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr900844q
更新日期：2010-02-05 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr301056q
更新日期：2013-03-01 00:00:00
abstract：:The purpose of this discovery phase study was to identify candidate protein biomarkers for high-grade dysplastic cervical cells using mass spectrometry. Laser Capture Microdissection (LCM) was utilized to isolate high-grade dysplastic and normal cells from ThinPrep slides prepared from cervical cytological specimens. ...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr070319j
更新日期：2007-11-01 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr1009383
更新日期：2011-03-04 00:00:00
abstract：:Triply and doubly charged iTRAQ ( isobaric tagging for relative and absolute quantitation) labeled peptide cations from a tryptic peptide mixture of bovine carbonic anhydrase II were subjected to electron transfer ion/ion reactions to investigate the effect of charge bearing modifications associated with iTRAQ on the ...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr8001113
更新日期：2008-09-01 00:00:00
abstract：:One application of 2D gel electrophoresis is to reveal differences in protein pattern between two or more groups of individuals, attributable to their group membership. Multivariate data analytical methods are useful in pinpointing the spots relevant for discrimination by focusing not only on single spot differences, ...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr700800s
更新日期：2008-03-01 00:00:00
abstract：:Pathogenic events in Alzheimer's disease are believed to involve an imbalance between the production and clearance of the neurotoxic 42 amino acid form of the beta-amyloid peptide (Abeta1-42). Although much is known about the production of Abeta1-42, many questions remain about its degradation. Here, we describe an op...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr0703627
更新日期：2007-11-01 00:00:00
abstract：:Mitosis is a highly regulated process in which errors can lead to genomic instability, a hallmark of cancer. During this phase of the cell cycle, transcription is silent and RNA translation is inhibited. Thus, mitosis is largely driven by post-translational modification of proteins, including phosphorylation, methylat...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr100281h
更新日期：2010-09-03 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr060406w
更新日期：2007-02-01 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr800485c
更新日期：2009-02-01 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr301190g
更新日期：2013-04-05 00:00:00
abstract：:Workflows for large-scale (MS)-based shotgun proteomics can potentially lead to costly errors in the form of incorrect peptide-spectrum matches (PSMs). To improve the robustness of these workflows, we have investigated the use of the precursor mass discrepancy (PMD) to detect and filter potentially false PSMs that hav...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.9b00478
更新日期：2020-01-03 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr8003024
更新日期：2008-10-01 00:00:00
abstract：:Pinus radiata is one of the most economically important forest tree species, with a worldwide production of around 370 million m (3) of wood per year. Current selection of elite trees to be used in conservation and breeding programes requires the physiological and molecular characterization of available populations. T...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr7006285
更新日期：2008-07-01 00:00:00
abstract：:Tumor invasion defines the transition between tissue-restricted carcinomas, related to good outcome as optimal surgery becomes possible, and metastatic tumors associated with poor prognosis and a dramatic decrease in survival. In endometrial cancer, myometrial infiltration represents a determinant parameter highly val...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr900390t
更新日期：2009-10-01 00:00:00
abstract：:The abundant proteins in human milk have been well characterized and are known to provide nutritional, protective, and developmental advantages to both term and preterm infants. However, relatively little is known about the expression of the low abundance proteins that are present in human milk because of the technica...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr2008797
更新日期：2012-03-02 00:00:00
abstract：:Src family kinases (SFKs) are the earliest known family of tyrosine kinases and are widely thought to play essential roles in cellular signal transduction. Although numerous functional analyses have been performed, no study has analyzed the specificity of all SFKs on an equal platform. To gain a better understanding o...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr100773t
更新日期：2010-11-05 00:00:00
