Receptor for Advanced Glycation End Products (RAGE) Functions as Receptor for Specific Sulfated Glycosaminoglycans, and Anti-RAGE Antibody or Sulfated Glycosaminoglycans Delivered in Vivo Inhibit Pulmonary Metastasis of Tumor Cells

Mizumoto, Shuji; Takahashi, J.; Sugahara, Kazuyuki

doi:10.1074/jbc.m111.313437

Cited by 95 publications

(92 citation statements)

References 50 publications

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“…These heparins with low anticoagulant activity were also able to prevent metastases 77 . Altered expression of chondroitin sulfate (CS -with higher proportion of E-disaccharide units) on the surface of tumor cells may contribute to malignant transformation and metastasis which canbe inhibited in lung cancer cells by pre-administration of CS-E from squid cartilage rich in E units or antibodies against CS-E interfering with CS-RAGE signaling suggesting a putative role of these approaches in the treatment of pulmonary metastasis 78 . AGEs induced proliferation of breast cancer cells could be completely prevented by anti-RAGE antibodies 23 .…”

Section: Targeting Rage and Its Ligands -Can It Contribute To The Trementioning

confidence: 99%

HMGB1, S100 proteins and other RAGE ligands in cancer - markers, mediators and putative therapeutic targets

et al. 2016

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Background and Aims. Activation of RAGE due to its increased expression in cancer cells or its stimulation by multiple ligands (AGEs, HMGB1, S100 proteins, etc.) may contribute to the proliferation, invasiveness of tumor cells and formation of distant metastases and also to the resistance of cancer to treatment. RAGE ligands could thus become both useful markers of disease severity and its outcome and, a potential therapeutic target. Conclusions. Better understanding of the role of RAGE activation in different types of cancer may help to define the role of ligand/RAGE antagonists as promising cancer treatment.

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Section: Targeting Rage and Its Ligands -Can It Contribute To The Trementioning

confidence: 99%

HMGB1, S100 proteins and other RAGE ligands in cancer - markers, mediators and putative therapeutic targets

et al. 2016

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“…A decrease in heparan sulfate level is related to lung hypoplasia and other developmental malformations with increased perinatal mortality [92,93]. In the lung, glycosaminoglycans and heparan sulfate bind strongly to RAGE and RAGE ligands such as HMGB1 [19,20,94]. Thus it is highly likely that the observed adhesion of lung epithelial cells with basal lamina is achieved by the electrostatic interactions exerted between RAGE and basal lamina glycosaminoglycans and heparin sulfate chains.…”

Section: Normal Rage Expression Suppressed Rage Expressionmentioning

confidence: 99%

“…What may be more feasible as a therapeutic intervention is the prevention and treatment of lung metastatic disease arising from other primary tumors, such as melanoma. Both in vitro and in vivo studies demonstrate that ligand-RAGE axis inactivation restricts metastatic formation to the lung [19,20,[112][113][114].…”

Section: Rage As a Potential Target Of Therapeutic Intervention: Evidmentioning

confidence: 99%

“…In vivo studies have shown that glycosaminoglycan-RAGE interactions are promising targets in the prevention and management of pulmonary metastases [19,20]. Administration of the derivative 2-O, 3-O-desulfated heparin significantly reduces the formation of lung metastasis after intravenous injection of melanoma cells [113].…”

Section: Rage As a Potential Target Of Therapeutic Intervention: Evidmentioning

confidence: 99%

“…However, nowadays, the list of RAGE ligands has been significantly extended, with RAGE acting either as a receptor or as an adhesion molecule [13], being able to bind to amphoterin, S100 proteins, integrin Mac-1, collagen IV, amyloid-β and amyloid A peptides, glycosaminoglycans and others [5,6,[13][14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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Critical role of RAGE in lung physiology and tumorigenesis: a potential target of therapeutic intervention?

Marinakis

Bagkos

Piperi

et al. 2014

Clinical Chemistry and Laboratory Medicine (CCLM)

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Lung cancer is one of the most common malignancies in the world and one of the leading causes of death from cancer. In the search for molecules that may be involved in lung tumor induction and progression, the receptor of advanced glycation end products (RAGE) comes across as a critical regulator of lung physiology. RAGE is a multiligand receptor that presents a differential expression pattern in lung epithelial cells compared to other cell types being gradually increased from fetal to birth and adult life. Under stress conditions, RAGE expression and activation are rapidly elevated resulting in chronic inflammation, which, in turn, in many instances, promotes epithelial cell malignant transformation. RAGE overexpression in normal lung alveolar type I epithelial cells is followed by rapid downregulation upon malignant transformation, being associated with increased aggressiveness. This is a striking paradox, since in every other cell type the pattern of RAGE expression follows the opposite direction, suggesting the involvement of RAGE in the well-functioning of lung cells. Additionally, RAGE has been attributed with the role of adhesion molecule, since it can stabilize mature alveolar epithelial cells to their substrate (basal lamina) by interacting electrostatically with other molecules. However, the reduction of RAGE observed in lung tumorigenesis interrupts cell-to-cell and cell-to-substrate communication, which is a critical step for cancer cell induction, progression and migration. This review addresses the differential properties of RAGE in lung physiology and carcinogenesis, providing evidence of therapeutic possibilities.

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Identification of EGFR expression status association with metastatic lymph node density (ND) by expression microarray analysis of advanced gastric cancer

et al. 2014

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Metastatic lymph node density (ND) has been reproducibly proven to be a prognostic factor in gastric cancer. The molecular mechanisms that underlie this aggressiveness are underexplored. Here, we aimed to identify molecules associated with this unique phenotype. Tumor specimens from patients with stage III gastric cancer with high or low ND (n = 4 for both) were compared at the mRNA level using Affymetrix microarray (harboring 54,675 genes). The expression data were prioritized, and genes that correlated with ND were selected. Ultimately, the EGFR was validated as such a candidate molecule in patients with primary advanced gastric cancer who underwent standard treatment (n = 167). Expression data of the microarray were prioritized based on gene expression ratio and frequency of gene expression. The first priority genes to be selected were genes that are known to be amplified in cancer, which included NKX2.1, CHST9, CTNND2, SLC25A27, FGFR2, EGFR, and PTGER1. Of these genes, the EGFR gene was of particular interest. EGFR expression in primary gastric cancer was examined using immunohistochemistry (IHC). The Student's t-test elucidated a significant difference in EGFR expression between IHC 2+/3+ and IHC 1+ according to ND (P = 0.0035). The Chi-square test also indicated a significant difference between high and low levels of EGFR immunohistochemical staining (IHC2+/3+ and IHC1+, respectively) and ND status (P = 0.0023). According to the least squares method, as ND increased, the risk that EGFR staining levels changed from IHC 1+ to IHC 2+ also increased. In this study, we determined that high EGFR expression may underlie the aggressive mechanism of advanced gastric cancer with high ND.

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Receptor for Advanced Glycation End Products (RAGE) Functions as Receptor for Specific Sulfated Glycosaminoglycans, and Anti-RAGE Antibody or Sulfated Glycosaminoglycans Delivered in Vivo Inhibit Pulmonary Metastasis of Tumor Cells

Cited by 95 publications

References 50 publications

HMGB1, S100 proteins and other RAGE ligands in cancer - markers, mediators and putative therapeutic targets

HMGB1, S100 proteins and other RAGE ligands in cancer - markers, mediators and putative therapeutic targets

Critical role of RAGE in lung physiology and tumorigenesis: a potential target of therapeutic intervention?

Identification of EGFR expression status association with metastatic lymph node density (ND) by expression microarray analysis of advanced gastric cancer

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