International Journal of Molecular Sciences

Editorial

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3 pages, 189 KiB

Open AccessEditorial

Proteomics and Its Applications in Cancers

by Stanislav Naryzhny

Int. J. Mol. Sci. 2023, 24(5), 4457; https://doi.org/10.3390/ijms24054457 - 24 Feb 2023

Viewed by 1060

Abstract

Cancer is a system malignant transformation that covers a wide group of diseases and can affect any organ of the human body [...] Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Cancers)

Research

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35 pages, 1352 KiB

Open AccessArticle

Construction of 2DE Patterns of Plasma Proteins: Aspect of Potential Tumor Markers

by Stanislav Naryzhny, Natalia Ronzhina, Elena Zorina, Fedor Kabachenko, Nikolay Klopov and Victor Zgoda

Int. J. Mol. Sci. 2022, 23(19), 11113; https://doi.org/10.3390/ijms231911113 - 21 Sep 2022

Cited by 3 | Viewed by 1995

Abstract

The use of tumor markers aids in the early detection of cancer recurrence and prognosis. There is a hope that they might also be useful in screening tests for the early detection of cancer. Here, the question of finding ideal tumor markers, which [...] Read more.

The use of tumor markers aids in the early detection of cancer recurrence and prognosis. There is a hope that they might also be useful in screening tests for the early detection of cancer. Here, the question of finding ideal tumor markers, which should be sensitive, specific, and reliable, is an acute issue. Human plasma is one of the most popular samples as it is commonly collected in the clinic and provides noninvasive, rapid analysis for any type of disease including cancer. Many efforts have been applied in searching for “ideal” tumor markers, digging very deep into plasma proteomes. The situation in this area can be improved in two ways—by attempting to find an ideal single tumor marker or by generating panels of different markers. In both cases, proteomics certainly plays a major role. There is a line of evidence that the most abundant, so-called “classical plasma proteins”, may be used to generate a tumor biomarker profile. To be comprehensive these profiles should have information not only about protein levels but also proteoform distribution for each protein. Initially, the profile of these proteins in norm should be generated. In our work, we collected bibliographic information about the connection of cancers with levels of “classical plasma proteins”. Additionally, we presented the proteoform profiles (2DE patterns) of these proteins in norm generated by two-dimensional electrophoresis with mass spectrometry and immunodetection. As a next step, similar profiles representing protein perturbations in plasma produced in the case of different cancers will be generated. Additionally, based on this information, different test systems can be developed. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Cancers)

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16 pages, 3708 KiB

Open AccessArticle

An Integrated Proteomic and Glycoproteomic Investigation Reveals Alterations in the N-Glycoproteomic Network Induced by 2-Deoxy-D-Glucose in Colorectal Cancer Cells

by Cheng Ma, Hong-Yuan Tsai, Qi Zhang, Lakmini Senavirathna, Lian Li, Lih-Shen Chin, Ru Chen and Sheng Pan

Int. J. Mol. Sci. 2022, 23(15), 8251; https://doi.org/10.3390/ijms23158251 - 26 Jul 2022

Cited by 3 | Viewed by 2913

Abstract

As a well-known glycolysis inhibitor for anticancer treatment, 2-Deoxy-D-glucose (2DG) inhibits the growth and survival of cancer cells by interfering with the ATP produced by the metabolism of D-glucose. In addition, 2DG inhibits protein glycosylation in vivo by competing with D-mannose, leading to [...] Read more.

As a well-known glycolysis inhibitor for anticancer treatment, 2-Deoxy-D-glucose (2DG) inhibits the growth and survival of cancer cells by interfering with the ATP produced by the metabolism of D-glucose. In addition, 2DG inhibits protein glycosylation in vivo by competing with D-mannose, leading to endoplasmic reticulum (ER) stress and unfolded protein responses in cancer cells. However, the molecular details underlying the impact of 2DG on protein glycosylation remain largely elusive. With an integrated approach to glycoproteomics and proteomics, we characterized the 2DG-induced alterations in N-glycosylation, as well as the cascading impacts on the whole proteome using the HT29 colorectal cancer cell line as a model system. More than 1700 site-specific glycoforms, represented by unique intact glycopeptides (IGPs), were identified. The treatment of 2DG had a broad effect on the N-glycoproteome, especially the high-mannose types. The glycosite occupancy of the high-mannose N-glycans decreased the most compared with the sialic acid and fucose-containing N-glycans. Many of the proteins with down-regulated high-mannose were implicated in functional networks related to response to topologically incorrect protein, integrin-mediated signaling, lysosomal transport, protein hydroxylation, vacuole, and protein N-glycosylation. The treatment of 2DG also functionally disrupted the global cellular proteome, evidenced by significant up-regulation of the proteins implicated in protein folding, endoplasmic reticulum, mitochondrial function, cellular respiration, oxidative phosphorylation, and translational termination. Taken together, these findings reveal the complex changes in protein glycosylation and expression underlying the various effects of 2DG on cancer cells, and may provide insightful clues to inform therapeutic development targeting protein glycosylation. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Cancers)

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22 pages, 2800 KiB

Open AccessArticle

Haptoglobin Induces a Specific Proteomic Profile and a Mature-Associated Phenotype on Primary Human Monocyte-Derived Dendritic Cells

by Alfredo Torres, Sheilah Vivanco, Francisca Lavín, Cristián Pereda, Alexey Chernobrovkin, Alejandra Gleisner, Marcela Alcota, Milton Larrondo, Mercedes N. López, Flavio Salazar-Onfray, Roman A. Zubarev and Fermín E. González

Int. J. Mol. Sci. 2022, 23(13), 6882; https://doi.org/10.3390/ijms23136882 - 21 Jun 2022

Cited by 5 | Viewed by 2000

Abstract

Damage-associated molecular patterns (DAMPs) play a critical role in dendritic cells (DCs) ability to trigger a specific and efficient adaptive immune response for different physiological and pathological scenarios. We have previously identified constitutive DAMPs (HMGB1 and Calreticulin) as well as new putative inducible [...] Read more.

Damage-associated molecular patterns (DAMPs) play a critical role in dendritic cells (DCs) ability to trigger a specific and efficient adaptive immune response for different physiological and pathological scenarios. We have previously identified constitutive DAMPs (HMGB1 and Calreticulin) as well as new putative inducible DAMPs such as Haptoglobin (HP), from a therapeutically used heat shock-conditioned melanoma cell lysate (called TRIMEL). Remarkably, HP was shown to be the most abundant protein in the proteomic profile of heat shock-conditioned TRIMEL samples. However, its relative contribution to the observed DCs phenotype has not been fully elucidated. Human DCs were generated from monocytes isolated from PBMC of melanoma patients and healthy donors. DC lineage was induced with rhIL-4 and rhGM-CSF. After additional stimulation with HP, the proteome of these HP-stimulated cells was characterized. In addition, DCs were phenotypically characterized by flow cytometry for canonical maturation markers and cytokine production. Finally, in vitro transmigration capacity was assessed using Transwell plates. Our results showed that the stimulation with HP was associated with the presence of exclusive and higher relative abundance of specific immune-; energy production-; lipid biosynthesis-; and DAMPs-related proteins. Importantly, HP stimulation enhanced the expression of specific DC maturation markers and pro-inflammatory and Th1-associated cytokines, and an in vitro transmigration of primary human DCs. Taken together, these data suggest that HP can be considered as a new inducible DAMP with an important role in in vitro DC activation for cancer immunotherapy. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Cancers)

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19 pages, 3200 KiB

Open AccessArticle

Combining Recombinase-Mediated Cassette Exchange Strategy with Quantitative Proteomic and Phosphoproteomic Analyses to Inspect Intracellular Functions of the Tumor Suppressor Galectin-4 in Colorectal Cancer Cells

by Malwina Michalak, Viola Golde, Dominik Helm, Herbert Kaltner, Johannes Gebert and Jürgen Kopitz

Int. J. Mol. Sci. 2022, 23(12), 6414; https://doi.org/10.3390/ijms23126414 - 8 Jun 2022

Cited by 4 | Viewed by 2115

Abstract

Galectin-4 (Gal4) has been suggested to function as a tumor suppressor in colorectal cancer (CRC). In order to systematically explore its function in CRC, we established a CRC cell line where Gal4 expression can be regulated via the doxycycline (dox)-inducible expression of a [...] Read more.

Galectin-4 (Gal4) has been suggested to function as a tumor suppressor in colorectal cancer (CRC). In order to systematically explore its function in CRC, we established a CRC cell line where Gal4 expression can be regulated via the doxycycline (dox)-inducible expression of a single copy wildtype LGALS4 transgene generated by recombinase-mediated cassette exchange (RMCE). Using this model and applying in-depth proteomic and phosphoproteomic analyses, we systematically screened for intracellular changes induced by Gal4 expression. Overall, 3083 cellular proteins and 2071 phosphosites were identified and quantified, of which 1603 could be matched and normalized to their protein expression levels. A bioinformatic analysis revealed that most of the regulated proteins and phosphosites can be localized in the nucleus and are categorized as nucleic acid-binding proteins. The top candidates whose expression was modulated by Gal4 are PURB, MAPKAPK3, BTF3 and BCAR1, while the prime candidates with altered phosphorylation included ZBTB7A, FOXK1, PURB and CK2beta. In order to validate the (phospho)proteomic data, we confirmed these candidates by a radiometric metabolic-labelling and immunoprecipitation strategy. All candidates exert functions in the transcriptional or translational control, indicating that Gal4 might be involved in these processes by affecting the expression or activity of these proteins. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Cancers)

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Review

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16 pages, 2359 KiB

Open AccessReview

The Influence of Proteins on Fate and Biological Role of Circulating DNA

by Oleg Tutanov and Svetlana Tamkovich

Int. J. Mol. Sci. 2022, 23(13), 7224; https://doi.org/10.3390/ijms23137224 - 29 Jun 2022

Cited by 4 | Viewed by 1624

Abstract

Circulating DNA has already proven itself as a valuable tool in translational medicine. However, one of the overlooked areas of circulating DNA research is its association with different proteins, despite considerable evidence that this association might impact DNA’s fate in circulation and its [...] Read more.

Circulating DNA has already proven itself as a valuable tool in translational medicine. However, one of the overlooked areas of circulating DNA research is its association with different proteins, despite considerable evidence that this association might impact DNA’s fate in circulation and its biological role. In this review, we attempt to shed light on current ideas about circulating DNA origins and forms of circulation, known biological effects, and the clinical potential of circulating tumor deoxyribonucleoprotein complexes. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Cancers)

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19 pages, 1381 KiB

Open AccessReview

Single-Cell Proteomics: The Critical Role of Nanotechnology

by Carlota Arias-Hidalgo, Pablo Juanes-Velasco, Alicia Landeira-Viñuela, Marina L. García-Vaquero, Enrique Montalvillo, Rafael Góngora, Ángela-Patricia Hernández and Manuel Fuentes

Int. J. Mol. Sci. 2022, 23(12), 6707; https://doi.org/10.3390/ijms23126707 - 16 Jun 2022

Cited by 8 | Viewed by 3928

Abstract

In single-cell analysis, biological variability can be attributed to individual cells, their specific state, and the ability to respond to external stimuli, which are determined by protein abundance and their relative alterations. Mass spectrometry (MS)-based proteomics (e.g., SCoPE-MS and SCoPE2) can be used [...] Read more.

In single-cell analysis, biological variability can be attributed to individual cells, their specific state, and the ability to respond to external stimuli, which are determined by protein abundance and their relative alterations. Mass spectrometry (MS)-based proteomics (e.g., SCoPE-MS and SCoPE2) can be used as a non-targeted method to detect molecules across hundreds of individual cells. To achieve high-throughput investigation, novel approaches in Single-Cell Proteomics (SCP) are needed to identify and quantify proteins as accurately as possible. Controlling sample preparation prior to LC-MS analysis is critical, as it influences sensitivity, robustness, and reproducibility. Several nanotechnological approaches have been developed for the removal of cellular debris, salts, and detergents, and to facilitate systematic sample processing at the nano- and microfluidic scale. In addition, nanotechnology has enabled high-throughput proteomics analysis, which have required the improvement of software tools, such as DART-ID or DO-MS, which are also fundamental for addressing key biological questions. Single-cell proteomics has many applications in nanomedicine and biomedical research, including advanced cancer immunotherapies or biomarker characterization, among others; and novel methods allow the quantification of more than a thousand proteins while analyzing hundreds of single cells. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Cancers)

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Other

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19 pages, 14741 KiB

Open AccessPerspective

Changing Landscape of Cancer Vaccines—Novel Proteomics Platform for New Antigen Compositions

by Petr G. Lokhov, Steven Lichtenberg and Elena E. Balashova

Int. J. Mol. Sci. 2022, 23(8), 4401; https://doi.org/10.3390/ijms23084401 - 15 Apr 2022

Cited by 2 | Viewed by 2856

Abstract

The creation of cancer vaccines is a constant priority for research and biotechnology. Therefore, the emergence of any new technology in this field is a significant event, especially because previous technologies have not yielded results. Recently, the development of a cancer vaccine has [...] Read more.

The creation of cancer vaccines is a constant priority for research and biotechnology. Therefore, the emergence of any new technology in this field is a significant event, especially because previous technologies have not yielded results. Recently, the development of a cancer vaccine has been complemented by a new proteomics technology platform that allows the creation of antigen compositions known as antigenic essences. Antigenic essence comprises a target fraction of cellular antigens, the composition of which is precisely controlled by peptide mass spectrometry and compared to the proteomic footprint of the target cells to ensure similarity. This proteomics platform offers potential for a massive upgrade of conventional cellular cancer vaccines. Antigenic essences have the same mechanism of action, but without the disadvantages, and with notable advantages such as precise targeting of the immune response, safety, controlled composition, improved immunogenicity, addressed MHC restriction, and extended range of vaccination doses. The present paper calls attention to this novel platform, stimulates discussion of the role of antigenic essence in vaccine development, and consolidates academic science with biotech capabilities. A brief description of the platform, list of cellular cancer vaccines suitable for the upgrade, main recommendations, limitations, and legal and ethical aspects of vaccine upgrade are reported here. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Cancers)

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