Changes of protein glycosylation in the course of radiotherapy

Tóth, Eszter; Vékey, Károly; Ozohanics, Olivér; Jekő, Anita; Domińczyk, Iwona; Widłak, Piotr; Drahos, László

doi:10.1016/j.jpba.2015.11.010

Cited by 17 publications

(11 citation statements)

References 30 publications

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“…Surprisingly, the existence and role of such protein modifications of endothelium in response to ionizing radiation have never been investigated. We and others previously showed that glycosylation of serum proteins is deeply modified in response to localized dorsal radiation injury 16 and to radiation therapy 17 . These modifications could occur through modifications in expression of genes involved in glycosylation in the liver 16 .…”

Section: Introductionmentioning

confidence: 95%

Radiation-induced changes in the glycome of endothelial cells with functional consequences

Jaillet¹,

Morelle²,

Slomianny³

et al. 2017

Sci Rep

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As it is altered by ionizing radiation, the vascular network is considered as a prime target in limiting normal tissue damage and improving tumor control in radiation therapy. Irradiation activates endothelial cells which then participate in the recruitment of circulating cells, especially by overexpressing cell adhesion molecules, but also by other as yet unknown mechanisms. Since protein glycosylation is an important determinant of cell adhesion, we hypothesized that radiation could alter the glycosylation pattern of endothelial cells and thereby impact adhesion of circulating cells. Herein, we show that ionizing radiation increases high mannose-type N-glycans and decreases glycosaminoglycans. These changes stimulate interactions measured under flow conditions between irradiated endothelial cells and monocytes. Targeted transcriptomic approaches in vitro in endothelial cells and in vivo in a radiation enteropathy mouse model confirm that genes involved in N- and O-glycosylation are modulated by radiation, and in silico analyses give insight into the mechanism by which radiation modifies glycosylation. The endothelium glycome may therefore be considered as a key therapeutic target for modulating the chronic inflammatory response observed in healthy tissues or for participating in tumor control by radiation therapy.

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Section: Introductionmentioning

confidence: 95%

Radiation-induced changes in the glycome of endothelial cells with functional consequences

Jaillet¹,

Morelle²,

Slomianny³

et al. 2017

Sci Rep

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“…For example, Toth et al (2016) analysed glycosylation of seven common serum glycoproteins in head and neck cancer patients undergoing radiotherapy, using mass spectrometry, over a period of up to 15 months. They found varied and complex changes in the glycoforms of the proteins over time, which appeared to result from the effects of radiation and which returned to "normal" over time [110]. Such changes undoubtedly represent cellular responses and adaptations following injury, damage, and cell death due to radiation, but the functional implications of such changes to cancer biology and metastasis, if any, are not understood.…”

Section: The Effect Of Radiation On Normal and Cancer Cell Glycosylationmentioning

confidence: 99%

Does Direct and Indirect Exposure to Ionising Radiation Influence the Metastatic Potential of Breast Cancer Cells

Kadhim

Mayah

Brooks

2020

Cancers

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Ionising radiation (IR) is commonly used for cancer therapy; however, its potential influence on the metastatic ability of surviving cancer cells exposed directly or indirectly to IR remains controversial. Metastasis is a multistep process by which the cancer cells dissociate from the initial site, invade, travel through the blood stream or lymphatic system, and colonise distant sites. This complex process has been reported to require cancer cells to undergo epithelial-mesenchymal transition (EMT) by which the cancer cells convert from an adhesive, epithelial to motile, mesenchymal form and is also associated with changes in glycosylation of cell surface proteins, which may be functionally involved in metastasis. In this paper, we give an overview of metastatic mechanisms and of the fundamentals of cancer-associated glycosylation changes. While not attempting a comprehensive review of this wide and fast moving field, we highlight some of the accumulating evidence from in vitro and in vivo models for increased metastatic potential in cancer cells that survive IR, focusing on angiogenesis, cancer cell motility, invasion, and EMT and glycosylation. We also explore the indirect effects in cells exposed to exosomes released from irradiated cells. The results of such studies need to be interpreted with caution and there remains limited evidence that radiotherapy enhances the metastatic capacity of cancers in a clinical setting and undoubtedly has a very positive clinical benefit. However, there is potential that this therapeutic benefit may ultimately be enhanced through a better understanding of the direct and indirect effects of IR on cancer cell behaviour.

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“…Protein Variants-Protein variants are commonly detected in proteomic analysis and include post-translational modifications such as phosphorylation (31), glycosylation (32), and acetylation (33). Consistently, in the present study, variants were detected for ϳ40% of proteins, and most of the variants had the same isoelectric points (pI) and molecular masses (MW); a similar variation trend was found while comparing Wt, P, and T, indicating that the expression levels of most of these proteins were mainly regulated at the transcriptional or posttranscriptional stage or at the degradation stage, with similar mechanisms.…”

Section: Fig 2 Different Protein Expression Spots Identified By 2d-mentioning

confidence: 99%

Differential Proteomic Analysis of Gender-dependent Hepatic Tumorigenesis in Hras12V Transgenic Mice

Rong

Fan

et al. 2017

Molecular & Cellular Proteomics

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Male prevalence is an outstanding characteristic of hepatocellular carcinoma (HCC), and the underlying mechanisms for this have remained largely unknown. In the present study, Hras12V transgenic mice, in which hepatocyte-specific expression of the oncogene induces male-biased hepatic tumorigenesis, were studied, and altered proteins were detected by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). Protein samples from hepatic tumor tissues (T) and peritumor tissues (P) of transgenic males and females and the corresponding normal liver tissues (Wt) of nontransgenic males and females were subjected to pairwise comparisons based on proteomic analysis. Among 2381 autodetected protein spots, more than 1600 were differentially expressed based on a pairwise comparison (|ratio|> = 1.5, < = 0.05). Of these, 180 spots were randomly selected for matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS) identification; finally, 89 distinct proteins were obtained. Among these 89 proteins, 7 and 50 proteins were further validated by Western blotting and literature investigation, respectively. Intriguingly, compared with Wt, the altered proteins were relatively concentrated in T in transgenic females but in P in transgenic males. Consistently, the levels of p-ERK and p-mTOR were significantly higher in the T of females compared with that of males. The pathway enrichment assay showed that 5 pathways in males but only 1 in females were significantly altered in terms of the upregulated proteins in T compared with Wt. These data indicate that female hepatocytes are disturbed by oncogenes with great difficulty, whereas male hepatocytes readily do so. In addition, 33 proteins were gender-dependently altered in hepatic tumorigenesis. Moreover, 4% DNA packaging and 4% homeostasis-related functional proteins were found in females but not in males, and more nucleus proteins were found in females (8%) than in males (3%). In conclusion, the proteomic data and comparative analysis presented here offer crucial clues for elucidating the mechanisms that underlie the male prevalence in HCC.

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Changes of protein glycosylation in the course of radiotherapy

Cited by 17 publications

References 30 publications

Radiation-induced changes in the glycome of endothelial cells with functional consequences

Radiation-induced changes in the glycome of endothelial cells with functional consequences

Does Direct and Indirect Exposure to Ionising Radiation Influence the Metastatic Potential of Breast Cancer Cells

Differential Proteomic Analysis of Gender-dependent Hepatic Tumorigenesis in Hras12V Transgenic Mice

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