Rage signalling promotes intestinal tumourigenesis

Heijmans, Jarom; Büller, Nikè V. J. A.; Hoff, Eva; Dihal, Ashwin A.; Poll, Tom van der; Zoelen, Marieke A. D. van; Bierhaus, Angelika; Biemond, I.; Hardwick, James C.H.; Hommes, Daniël W.; Muncan, Vanesa; Brink, Gijs R. van den

doi:10.1038/onc.2012.119

Cited by 49 publications

(49 citation statements)

References 27 publications

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“…RAGE has been identified in both epithelial and mesenchymal cells and is upregulated in intestinal adenomas (27). In RAGE-knockout mice, tumor cells showed increased apoptosis and intestinal tumorigenesis was reduced (28). All these findings support our observation that serum VAP-1 is associated with incident cancers in the present study.…”

Section: <00001 Aceis or Arbs (N %)supporting

confidence: 82%

Serum Vascular Adhesion Protein-1 Level Predicts Risk of Incident Cancers in Subjects with Type II Diabetes

Yin

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Serum vascular adhesion protein-1 (VAP-1) predicts cancer-related mortality in diabetic subjects. However, whether serum VAP-1 predicts cancer incidence or cancer progression remains unclear. We conducted a cohort study to investigate whether serum VAP-1 and related clinical variables predict incident cancers in type II diabetic subjects.Methods: From 1996 to 2003, we enrolled 568 type II diabetic subjects who were free of cancer at baseline. Serum VAP-1 at enrollment was measured by time-resolved immunofluorometric assay. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m

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Section: <00001 Aceis or Arbs (N %)supporting

confidence: 82%

Serum Vascular Adhesion Protein-1 Level Predicts Risk of Incident Cancers in Subjects with Type II Diabetes

Yin

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…13,24 RAGE is a critical mediator of pancreatic carcinogenesis through its ability to amplify interleukin (IL)-6-induced autophagic translocation of signal transducer and activator of transcription (STAT)3 to the mitochondria and enhance ATP production.…”

Section: Introductionmentioning

confidence: 99%

“…23 RAGE binds multiple ligands derived from a damaged cell environment including HMGB1 and S100 protein. 13,24 RAGE is a critical mediator of pancreatic carcinogenesis through its ability to amplify interleukin (IL)-6-induced autophagic translocation of signal transducer and activator of transcription (STAT)3 to the mitochondria and enhance ATP production. 25 Blockade of HMGB1 and RAGE suppressed tumor growth and metastasis in a murine model of lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic lymphocytic leukemia

Clear

Liu

et al. 2014

Blood

104

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Key Points• HMGB1 and DNA released from CLL cells induce nurse-like cell differentiation.• This differentiation appears TLR9/RAGE dependent.Chronic lymphocytic leukemia (CLL) is a disease of an accumulation of mature B cells that are highly dependent on the microenvironment for maintenance and expansion. However, little is known regarding the mechanisms whereby CLL cells create their favorable microenvironment for survival. High-mobility group protein B-1 (HMGB1) is a highly conserved nuclear protein that can be actively secreted by innate immune cells and passively released by injured or dying cells. We found significantly increased HMGB1 levels in the plasma of CLL patients compared with healthy controls, and HMGB1 concentration is associated with absolute lymphocyte count. We therefore sought to determine potential roles of HMGB1 in modulating the CLL microenvironment. CLL cells passively released HMGB1, and the timing and concentrations of HMGB1 in the medium were associated with differentiation of nurse-like cells (NLCs). Higher CD68 expression in CLL lymph nodes, one of the markers for NLCs, was associated with shorter overall survival of CLL patients. HMGB1-mediated NLC differentiation involved internalization of both receptor for advanced glycation end products (RAGE) and Toll-like receptor-9 (TLR9). Differentiation of NLCs can be prevented by blocking the HMGB1-RAGE-TLR9 pathway. In conclusion, this study demonstrates for the first time that CLL cells might modulate their microenvironment by releasing HMGB1. (Blood. 2014;123(11):1709-1719 IntroductionMany cancers arise from sites of infection, chronic irritation, and inflammation. An inflammatory microenvironment is an important participant in the neoplastic process, fostering proliferation, survival, and migration for cancers, including chronic lymphocytic leukemia (CLL).1-4 Stressed, injured, or dying cells release damage-associated molecular patterns (DAMPs), which initiate noninfectious inflammatory responses. [5][6][7] The DAMP high-mobility group protein B1 (HMGB1) is a major player associating inflammation and cancer. 8,9 HMGB1 is a nuclear protein that can be released passively by damaged or dead cells or actively by immune cells and stressed cancer cells. [10][11][12][13][14] HMGB1 regulates transcription factors but also behaves as a proinflammatory cytokine mediating inflammation. 13,[15][16][17][18] Nonprotein DAMPs, including DNA, RNA, and ATP, are also released by damaged or dying cells. 6,7,19 DAMPs are associated with acute inflammatory responses, chronic inflammation, and wound healing, but are also important components of the disordered tumor microenvironment. 8,20 HMGB1 is a DNA-binding protein, and increased serum concentrations of the HMGB1-DNA complex can activate the immune system and cause systemic autoimmune disease via the receptor for advanced glycation end products (RAGE) and toll-like receptor-9 (TLR9). 21 Interactions of HMGB1-RAGE-TLR9 constitute a tripod that triggers nuclear factor kB (NF-kB) activation 22 and promotes ...

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“…Furthermore, tumor size was significantly smaller in the antibody treated group, suggesting that HMGB1 may also be one of the factors associated with inflammation-associated cancer [56]. Notably, the HMGB1 receptors, RAGE and TLRs, correlated with IBD tumorigenesis [57][58][59], and HMGB1 forms a stable complex with RAGE in protein extract derived from cancer cells but not normal tissues, showing the function of the HMGBA-RAGE axis in tumorigenesis [60]. In colon cancer cells, HMGB1 is phosphorylated at serines 35, 39, and 42, which are in the NLS sequence, and then transferred to the cytoplasm and secreted [61].…”

Section: Potential Role Of Hmgb1 In Ibd Neoplasiamentioning

confidence: 93%

Role of high-mobility group box 1 protein in inflammatory bowel disease

Wang

Gong

et al. 2015

Inflamm. Res.

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High-mobility group box 1 (HMGB1) protein is a nuclear non-histone DNA-binding protein. It is released into the extracellular milieu and mediates inflammatory responses, which contribute to the pathogenesis of numerous inflammatory diseases, including inflammatory bowel disease (IBD). An online search was performed in PubMed and Web of Science databases for articles providing evidence on the role of HMGB1 in IBD. HMGB1 plays an important role in IBD pathogenesis. Application of HMGB1 antagonists reduced inflammatory reactions and ameliorated colitis in rodent models, which may provide new insights into the diagnosis and treatment of IBD.

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Rage signalling promotes intestinal tumourigenesis

Cited by 49 publications

References 27 publications

Serum Vascular Adhesion Protein-1 Level Predicts Risk of Incident Cancers in Subjects with Type II Diabetes

Serum Vascular Adhesion Protein-1 Level Predicts Risk of Incident Cancers in Subjects with Type II Diabetes

Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic lymphocytic leukemia

Role of high-mobility group box 1 protein in inflammatory bowel disease

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