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

Jaillet, Cyprien; Morelle, Willy; Slomianny, Marie-Christine; Paget, Vincent; Tarlet, Georges; Buard, Valérie; Selbonne, Sonia; Caffin, Fanny; Rannou, Emilie; Martinez, Pierre; François, Agnès; Foulquier, François; Allain, Fabrice; Milliat, Fabien; Guipaud, Olivier

doi:10.1038/s41598-017-05563-y

Cited by 34 publications

(39 citation statements)

References 50 publications

(61 reference statements)

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“…Very little is known about potential changes in cancer cell glycosylation related to cell behaviour following radiation. Intriguingly, however, Jaillett et al (2017) showed overexpression of several polypeptide-N-acetylgalactosamine (GalNAc) transferases (GalNAc-Ts), the family of genes that mediate the attachment of the first GalNAc in O-linked glycosylation, by endothelial cells, in mouse intestine after radiation exposure [111]. As described previously, cancer cells frequently exhibit an increase in truncated O-glycans consistent with this type of general up-regulation in O-linked glycosylation.…”

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

confidence: 70%

“…They found an increase in high-mannose or oligomannose type N-glycans (these are glycans where the trimannosyl core is extended by mannose residues exclusively) and an increase in monocyte adhesion to endothelial cells, but were unable to demonstrate that the glycans were functional in this adhesion. They suggested that alterations in glycosylation may be a mechanism by which organisms regulate cell adhesion during inflammation, recovery, and healing after radiation exposure [111].…”

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

confidence: 99%

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

confidence: 70%

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

View full text Add to dashboard Cite

show abstract

“…Within these matured and normal vessels endothelial anergy is restored. Jaillet et al reported that ionizing radiation altered the glycosylation pattern of endothelial cells, in particular increased high mannose-type N-glycans and decreased glycosaminoglycans, which stimulated the interactions between irradiated endothelial cells and monocytes ( 108 ). Thus, targeting either the endothelium glycome may be considered as therapeutic target for modulating the inflammatory response or combining radiation therapy that seems to reduce endothelial anergy with anti-immunosuppressive therapy.…”

Section: Tumor Endothelium Mediated Immunological Consequences In Thementioning

confidence: 99%

The Tumor Vascular Endothelium as Decision Maker in Cancer Therapy

2018

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Genetic and pathophysiologic criteria prearrange the uncontrolled growth of neoplastic cells that in turn initiates new vessel formation, which is prerequisite for further tumor growth and progression. This first endothelial lining is patchy, disordered in structure and thus, angiogenic tumor vessels were proven to be functionally inferior. As a result, tumors were characterized by areas with an apparent oversupply in addition to areas with an undersupply of vessels, which complicates an efficient administration of intravenous drugs in cancer therapy and might even lower the response e.g. of radiotherapy (RT) because of the inefficient oxygen supply. In addition to the vascular dysfunction, tumor blood vessels contribute to the tumor escape from immunity by the lack of response to inflammatory activation (endothelial anergy) and by repression of leukocyte adhesion molecule expression. However, tumor vessels can remodel by the association with and integration of pericytes and smooth muscle cells which stabilize these immature vessels resulting in normalization of the vascular structures. This normalization of the tumor vascular bed could improve the efficiency of previously established therapeutic approaches, such as chemo- or radiotherapy by a more homogenous drug and oxygen distribution, and/or by overcoming endothelial anergy. This review highlights the current investigations that take advantage of a proper vascular function for improving cancer therapy with a special focus on the endothelial-immune system interplay.

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“…Lee et al confirmed that radiation exposure enhanced the sialylation of cellular proteins in colon cancer cells by fluorescence- activated cell sorting analysis 27 . Analyzing site-specific data of patients suffering from head and neck cancer, Toth et al observed that intensity of 44% of glycoforms increased and 56% decreasedin in the course of radiotherapy 24 .Targeted transcriptomic approaches in vitro in endothelial cells and in vivo in a radiation enteropathy mouse model proved that genes involved in N- and O-glycosylation were altered by radiation 28 . In our work, mRNA and protein expression of C1GalT1 was induced by exposure to a low dose of radiation.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of C1GalT1 inhibits radioresistance of human esophageal cancer cells through modifying β1-integrin glycosylation

Zhang¹,

Deng²,

Qiu³

et al. 2018

J. Cancer

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Radiotherapy has played a limited role for the treatment of human esophageal cancer owing to the risk of tumor radioresistance. Core 1 β1, 3-galactosyltransferase (C1GalT1), which catalyzes the formation of core 1 O-glycan structures, is frequently overexpressed during tumorigenesis. However, the exact effects and mechanisms of C1GalT1 in the radioresistance of esophageal cancer remain unclear. In this study, Public databases and our data revealed that C1GalT1 expression was up-regulated in esophageal cancer tissues and was associated with poor survival. Upon irradiation, we found that esophageal cancer cells with high levels of C1GalT1 could tolerate cell death and had increased resistance to radiotherapy. Irradiation also promoted the expression of C1GalT1 and core 1 O-glycan structures. C1GalT1 knockdown increased the radiosensitivity of esophageal cancer cells, and attenuated irradiation-enhanced migration and invasion. Mechanistic investigations showed that C1GalT1 modified O-glycan structures on β1-integrin and regulated its downstream focal adhesion kinase (FAK) signaling. Furthermore, β1-integrin-blocking antibody and FAK inhibitor enhanced radiation-induced apoptosis in esophageal cancer cells. Together, our results indicate that C1GalT1 is a major determinant of radioresistance via modulation of β1-integrin glycosylation. C1GalT1 may be a potent molecular target for enhancing the efficacy of radiotherapy.

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

Cited by 34 publications

References 50 publications

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

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

The Tumor Vascular Endothelium as Decision Maker in Cancer Therapy

Knockdown of C1GalT1 inhibits radioresistance of human esophageal cancer cells through modifying β1-integrin glycosylation

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