AGEs, RAGEs and s-RAGE; friend or foe for cancer

Ahmad, Saheem; Khan, Hamda; Siddiqui, Zeba; Khan, Mohd Yasir; Rehman, Shahnawaz; Shahab, Uzma; Godovikova, Tatyana S.; Silnikov, Vladimir N.; Moinuddin, Mohammed

doi:10.1016/j.semcancer.2017.07.001

Cited by 154 publications

(108 citation statements)

References 136 publications

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“…Although less documented, the pathophysiology of cardiac disorders also seems to involve the RAGE signaling pathway 44 . Inflammation and cancer sharing many signaling pathways, the role of RAGE in carcinogenesis and the link with cell transformation, apoptosis and metastasis has been established 16,45,46 . Therefore, RAGE has become an attractive target for therapeutic purpose 7 .…”

Section: Discussionmentioning

confidence: 99%

“…RAGE is considered as a pattern recognition receptor, responding to danger signals and recognizing a three-dimensional structure rather than a specific amino acid sequence 11 . RAGE possesses ligand binding affinity for a wide range of molecules including Advanced Glycation End products (AGE) 12 , -amyloid peptide 13 , High mobility group box-1 (HMGB1) 14 or S100/calgranulins 15 [16][17][18][19] . Pro-inflammatory pathways such as nuclear factor kappa B (NF-B), mitogen-activated protein kinase (MAPK) or janus activated kinase/signal transducers and activators of transcription (JAK/STAT) are activated following engagement of RAGE 20 .…”

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confidence: 99%

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The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases

et al. 2019

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases

et al. 2019

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“…The name RAGE derives from its ability to bind advanced glycation end‐products (AGEs). Although a role for these major RAGE ligands has been tentatively proposed to explain the increased risk of various cancers (including PaC) in diabetic and obese individuals , surprisingly, their role in pancreatic carcinogenesis has never been investigated . AGEs comprise a heterogeneous group of compounds that accumulate in tissues of ageing individuals and, at an accelerated rate, in diabetic and obese subjects, owing to mechanisms including increased carbohydrate and lipid substrate availability, oxidative and non‐oxidative conditions favouring the glycation process, and impaired detoxification .…”

Section: Introductionmentioning

confidence: 99%

The advanced glycation end‐product N^ϵ‐carboxymethyllysine promotes progression of pancreatic cancer: implications for diabetes‐associated risk and its prevention

Menini

Iacobini

Latouliere

et al. 2018

The Journal of Pathology

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Diabetes is an established risk factor for pancreatic cancer (PaC), together with obesity, a Western diet, and tobacco smoking. The common mechanistic link might be the accumulation of advanced glycation end-products (AGEs), which characterizes all of the above disease conditions and unhealthy habits. Surprisingly, however, the role of AGEs in PaC has not been examined yet, despite the evidence of a tumour-promoting role of receptor for advanced glycation end-products (RAGE), the receptor for AGEs. Here, we tested the hypothesis that AGEs promote PaC through RAGE activation. To this end, we investigated the effects of the AGE N -carboxymethyllysine (CML) in human pancreatic ductal adenocarcinoma (PDA) cell lines and in a mouse model of Kras-driven PaC interbred with a bioluminescent model of proliferation. Tumour growth was monitored in vivo by bioluminescence imaging and confirmed by histology. CML promoted PDA cell growth and RAGE expression, in a concentration-dependent and time-dependent manner, and activated downstream tumourigenic signalling pathways. These effects were counteracted by RAGE antagonist peptide (RAP). Exogenous AGE administration to PaC-prone mice induced RAGE upregulation in pancreatic intraepithelial neoplasias (PanINs) and markedly accelerated progression to invasive PaC. At 11 weeks of age (6 weeks of CML treatment), PaC was observed in eight of 11 (72.7%) CML-treated versus one of 11 (9.1%) vehicle-treated [control (Ctr)] mice. RAP delayed PanIN development in Ctr mice but failed to prevent PaC promotion in CML-treated mice, probably because of competition with soluble RAGE for binding to AGEs and/or compensatory upregulation of the RAGE homologue CD166/ activated leukocyte cell adhesion molecule, which also favoured tumour spread. These findings indicate that AGEs modulate the development and progression of PaC through receptor-mediated mechanisms, and might be responsible for the additional risk conferred by diabetes and other conditions characterized by increased AGE accumulation. Finally, our data suggest that an AGE reduction strategy, instead of RAGE inhibition, might be suitable for the risk management and prevention of PaC. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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“…In this context, oxidative stress, inflammatory response, and endothelial dysfunction are linked by binding to receptors for AGE (RAGEs) [8].…”

Section: Introductionmentioning

confidence: 99%

Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects

Perrone

Giovino

Benny

et al. 2020

Oxidative Medicine and Cellular Longevity

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219

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The advanced glycation end products (AGEs) are organic molecules formed in any living organisms with a great variety of structural and functional properties. They are considered organic markers of the glycation process. Due to their great heterogeneity, there is no specific test for their operational measurement. In this review, we have updated the most common chromatographic, colorimetric, spectroscopic, mass spectrometric, and serological methods, typically used for the determination of AGEs in biological samples. We have described their signaling and signal transduction mechanisms and cell epigenetic effects. Although mass spectrometric analysis is not widespread in the detection of AGEs at the clinical level, this technique is highly promising for the early diagnosis and therapeutics of diseases caused by AGEs. Protocols are available for high-resolution mass spectrometry of glycated proteins although they are characterized by complex machine management. Simpler procedures are available although much less precise than mass spectrometry. Among them, immunochemical tests are very common since they are able to detect AGEs in a simple and immediate way. In these years, new methodologies have been developed using an in vivo novel and noninvasive spectroscopic methods. These methods are based on the measurement of autofluorescence of AGEs. Another method consists of detecting AGEs in the human skin to detect chronic exposure, without the inconvenience of invasive methods. The aim of this review is to compare the different approaches of measuring AGEs at a clinical perspective due to their strict association with oxidative stress and inflammation.

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AGEs, RAGEs and s-RAGE; friend or foe for cancer

Cited by 154 publications

References 136 publications

The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases

The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases

The advanced glycation end‐product N^ϵ‐carboxymethyllysine promotes progression of pancreatic cancer: implications for diabetes‐associated risk and its prevention

Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects

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AGEs, RAGEs and s-RAGE; friend or foe for cancer

Cited by 154 publications

References 136 publications

The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases

The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases

The advanced glycation end‐product Nϵ‐carboxymethyllysine promotes progression of pancreatic cancer: implications for diabetes‐associated risk and its prevention

Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects

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The advanced glycation end‐product N^ϵ‐carboxymethyllysine promotes progression of pancreatic cancer: implications for diabetes‐associated risk and its prevention