Variety and Dynamics of Proteoforms in the Human Proteome: Aspects of Markers for Hepatocellular Carcinoma

Naryzhny, Stanislav N.; Zgoda, Victor G.; Kopylov, Arthur T.; Petrenko, Elena; Kleist, Olga; Archakov, Alexander I.

doi:10.3390/proteomes5040033

Cited by 12 publications

(14 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MS (shotgun analysis) of exosomal proteins was performed according to the filteraided sample preparation (FASP) protocol [16,17]. Briefly, the proteins were digested with trypsin (Promega Trypsin Gold), and MS/MS analysis of resulting peptides was performed in duplicate using an Orbitrap Fusion Lumos MS (Thermo Scientific, USA) [18,19].The data were searched by Mascot 2.4.1 (http://www.matrixscience.com/). As a protein sequence database, NeXtProt (October 2014) was used.…”

Section: Enzymatic Modification and Analysis Of Plasma Exosomesmentioning

confidence: 99%

Functional Properties of Circulating Exosomes Mediated by Surface-Attached Plasma Proteins

Shtam¹,

Naryzhny²,

Kopylov³

et al. 2018

J Hematol

Self Cite

View full text Add to dashboard Cite

Background: Exosomes and other types of extracellular vesicles present an important component of circulating plasma. Exosomes released by endothelial and blood cells account for majority of plasma exosomal population; exosomes secreted by other cells might cross tissue-plasma barrier and reach circulating plasma as well. Definitely, exosomes of different cellular origins are different by content and function. However, exosomal surface membrane interacts with plasma components. This interaction may alter composition of exosomal surface and hence, provide these vesicles with new functional properties. This study was aimed to estimate composition and possible functional role of proteins attached on the surface of plasma exosomes. Methods: Here, extracellular vesicles from human plasma were isolated by ultracentrifugation and treated by trypsin. Trypsinized and native exosomes were analyzed by nanoparticle tracking analysis, Western blotting and quantitative high-resolution mass spectrometry. Results: Surface-attached proteins were removed from exosomes isolated from plasma of healthy donors by incubation with serine protease (trypsin). Treatment did not impact exosomes integrity while slightly reduced hydrodynamic radius. Mass spectrometry revealed 259 exosomal proteins; among them 79 proteins were completely removed and more than half of the proteins were partially removed by trypsinization. Gene ontology functional annotation revealed mostly extracellular locations of proteins cleaved from a surface of the plasma exosomes. Moreover, proteins cleaved from the exosome surface are supposed to be implicated into integrin-linked kinase (ILK), focal adhesion kinase (FAK) and other pathways connecting cell surface with intracellular signaling cascades. Conclusion: Taken together, our results demonstrate that a surface of circulating exosomes is decorated by plasma proteins, and these proteins can mask tissue-specific characteristic of the exosomal surface membrane and provide exosomes with new and uniform properties.

show abstract

Section: Enzymatic Modification and Analysis Of Plasma Exosomesmentioning

confidence: 99%

Functional Properties of Circulating Exosomes Mediated by Surface-Attached Plasma Proteins

Shtam¹,

Naryzhny²,

Kopylov³

et al. 2018

J Hematol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hepatocellular carcinoma (HCC) is one of the most common malignancies, with high incidence and mortality, especially among East Asian and sub‐Saharan African populations . Unfortunately, the efficacy of current therapeutic strategies for HCC is unsatisfactory , leading to poor prognosis and high recurrence rate after surgical resection of primary tumors . Exploring the molecular mechanisms responsible for the malignant behaviors of HCC cells is of great importance for the diagnosis or targeted intervention of HCC.…”

Section: Introductionmentioning

confidence: 99%

SOX11 regulates apoptosis and cell cycle in hepatocellular carcinoma via Wnt/β‐catenin signaling pathway

Chen

et al. 2018

Biotech and App Biochem

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high mortality. Identifying key molecules involved in the regulation of HCC development is of great clinical significance. SOX11 is a transcription factor belonging to group C of Sry-related high mobility group box family whose abnormal expression is frequently seen in many kinds of human cancers. Here, we noted that the expression of SOX11 was decreased in human HCC tumors compared with that in matched normal tissues. Overexpression of SOX11 promoted growth inhibition and apoptosis in HCC cell line HuH-7. Mechanistically, SOX11 enhanced the expression of nemo-like kinase and the phosphorylation of TCF4, thereby blunting the activation of oncogenic Wnt/β-catenin signaling pathway in HuH-7 cells. Finally, SOX11 was also found to sensitize HuH-7 cells to chemotherapy drugs cisplatin and 5-fluorouraci. Therefore, our study identifies SOX11 as a potential tumor suppressor in HCC and may hopefully be beneficial for the clinical diagnosis or treatment of HCC.

show abstract

“…The success of cancer immunotherapy relies on the existence of a high sensitive and high specific TAA. Currently, with respect to HCC, a number of TAAs have been identified: α -fetoprotein (AFP), New York esophageal squamous cell carcinoma-1 (NY-ESO-1), melanoma antigen gene (MAGE) family, glypican-3 (GPC3), and so on [ 17 ]. T cell responses targeting those TAAs in HCC patients can be generally observed; however, the subsequent clinical outcomes are not very satisfactory [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Construction and Characterization of Adenovirus Vectors Encoding Aspartate-β-Hydroxylase to Preliminary Application in Immunotherapy of Hepatocellular Carcinoma

Zhou

Liu

et al. 2018

Journal of Immunology Research

View full text Add to dashboard Cite

Dendritic cells (DCs) harboring tumor-associated antigen are supposed to be a potential immunotherapy for hepatocellular carcinoma (HCC). Aspartate-β-hydroxylase (AAH), an overexpressed tumor-associated cell surface protein, is considered as a promising biomarker and therapeutic target for HCC. In this study, we constructed adenovirus vector encoding AAH gene by gateway recombinant cloning technology and preliminarily explored the antitumor effects of DC vaccines harboring AAH. Firstly, the total AAH mRNA was extracted from human HCC tissues; the cDNA was amplified by RT-PCR, verified, and sequenced after TA cloning. Gateway technology was used and the obtained 18T-AAH was used as a substrate, to yield the final expression vector Ad-AAH-IRES2-EGFP. Secondly, bone marrow-derived DCs were infected by Ad-AAH-IRES2-EGFP to yield AAH-DC vaccines. Matured DCs were demonstrated by increased expression of CD11c, CD80, and MHC-II costimulatory molecules. A dramatically cell-killing effect of T lymphocytes coculturing with AAH-DCs on HepG2 HCC cell line was demonstrated by CCK-8 and FCM assays in vitro. More importantly, in an animal experiment, the lysis effect of cytotoxic T lymphocytes (CTLs) on HepG2 cells in the AAH-DC group was stronger than that in the control groups. In conclusion, the gateway recombinant cloning technology is a powerful method of constructing adenovirus vector, and the product Ad-AAH-IRES2-EGFP may present as a potential candidate for DC-based immunotherapy of HCC.

show abstract

Variety and Dynamics of Proteoforms in the Human Proteome: Aspects of Markers for Hepatocellular Carcinoma

Cited by 12 publications

References 44 publications

Functional Properties of Circulating Exosomes Mediated by Surface-Attached Plasma Proteins

Functional Properties of Circulating Exosomes Mediated by Surface-Attached Plasma Proteins

SOX11 regulates apoptosis and cell cycle in hepatocellular carcinoma via Wnt/β‐catenin signaling pathway

Construction and Characterization of Adenovirus Vectors Encoding Aspartate-β-Hydroxylase to Preliminary Application in Immunotherapy of Hepatocellular Carcinoma

Contact Info

Product

Resources

About