Endocan Is Upregulated on Tumor Vessels in Invasive Bladder Cancer Where It Mediates VEGF-A–Induced Angiogenesis

Roudnicky, Filip; Poyet, Cédric; Wild, Peter J.; Krampitz, Sarah; Negrini, Fabrizia; Huggenberger, Reto; Rogler, Anja; Stöhr, Robert; Hartmann, Arndt; Provenzano, Maurizio; Otto, Vivianne I.; Detmar, Michael

doi:10.1158/0008-5472.can-12-1855

Cited by 158 publications

(155 citation statements)

References 48 publications

Supporting

Mentioning

143

Contrasting

Order By: Relevance

“…29,30 Investigations in cultured blood vascular endothelial cells have revealed that endocan expression was stimulated by vascular endothelial growth factor A (VEGF-A) through the phosphorylation of its receptor. 31 We have also observed in an earlier study that AGE-HSA at the same concentration (2.0 mg/mL) up-regulates VEGF expression in HUVECs. Therefore, we can infer that the AGE-induced expression of ESM-1 in this study is accompanied by VEGF production also.…”

Section: Discussionsupporting

confidence: 75%

Glycated serum albumin stimulates expression of endothelial cell specific molecule-1 in human umbilical vein endothelial cells: Implication in diabetes mediated endothelial dysfunction

Nirala

Perumal

Gohil

2015

Diabetes and Vascular Disease Research

View full text Add to dashboard Cite

Pro-inflammatory conditions induced by products of protein glycation in diabetes substantially enhance the risk of endothelial dysfunction and related vascular complications. Endothelial cell specific molecule-1 (ESM-1) or endocan has been demonstrated as a potential biomarker in cancer and sepsis. Its role in diabetes-induced pathologies remains unknown. The expression of ESM-1 gene is under cytokine regulation, indicating its role in endothelium-dependent pathological disorders. In this study, we investigated the effect of advanced glycated human serum albumin (AGE-HSA) on the production of ESM-1. We show that AGE-HSA exerts a modulating role on the expression of ESM-1 in human umbilical vein endothelial cells. It up-regulates expression of ESM-1 protein in a dose-dependent manner which correlates with its messenger RNA (mRNA) transcription. RAGE and galectin-3, both AGE receptors, show antagonistic action on its expression. While gene silencing of RAGE has down-regulatory effect, that of galectin-3 has up-regulatory effect on AGE-induced expression of ESM-1. Inhibition of MAPKKK and JNK pathways did not alter the expression. In contrast, phosphatidylinositol 3 kinase (PI3K) inhibition significantly up-regulated ESM-1 expression. In conclusion, these results suggest that AGE-induced activation of human umbilical vein endothelial cells promotes formation of endocan which is an endothelial dysfunction marker and may be related to vascular disease in diabetes.

show abstract

Section: Discussionsupporting

confidence: 75%

Glycated serum albumin stimulates expression of endothelial cell specific molecule-1 in human umbilical vein endothelial cells: Implication in diabetes mediated endothelial dysfunction

Nirala

Perumal

Gohil

2015

Diabetes and Vascular Disease Research

View full text Add to dashboard Cite

show abstract

“…Although recent work has suggested the existence of such positive feedback loop for VEGF signaling in vitro, 47 the underlying mechanisms remained unclear. We now identify fibronectin and HSPG2 as potential interactors of Esm1, which are known to regulate VEGF signaling and bind to VEGF-A 165 but not VEGF-A 121 .…”

Section: Discussionmentioning

confidence: 99%

Esm1 Modulates Endothelial Tip Cell Behavior and Vascular Permeability by Enhancing VEGF Bioavailability

Rocha¹,

Schiller

Ding

et al. 2014

Circulation Research

179

166

View full text Add to dashboard Cite

Rationale: Endothelial cell–specific molecule 1 (Esm1) is a secreted protein thought to play a role in angiogenesis and inflammation. However, there is currently no direct in vivo evidence supporting a function of Esm1 in either of these processes. Objective: To determine the role of Esm1 in vivo and the underlying molecular mechanisms. Methods and Results: We generated and analyzed Esm1 knockout ( Esm1 KO ) mice to study its role in angiogenesis and inflammation. Esm1 expression is induced by the vascular endothelial growth factor A (VEGF-A) in endothelial tip cells of the mouse retina. Esm1 KO mice showed delayed vascular outgrowth and reduced filopodia extension, which are both VEGF-A–dependent processes. Impairment of Esm1 function led to a decrease in phosphorylated Erk1/2 (extracellular-signal regulated kinases 1/2) in sprouting vessels. We also found that Esm1 KO mice displayed a 40% decrease in leukocyte transmigration. Moreover, VEGF-induced vascular permeability was decreased by 30% in Esm1 KO mice and specifically on stimulation with VEGF-A 165 but not VEGF-A 121 . Accordingly, cerebral edema attributable to ischemic stroke–induced vascular permeability was reduced by 50% in the absence of Esm1. Mechanistically, we show that Esm1 binds directly to fibronectin and thereby displaces fibronectin-bound VEGF-A 165 leading to increased bioavailability of VEGF-A 165 and subsequently enhanced levels of VEGF-A signaling. Conclusions: Esm1 is simultaneously a target and modulator of VEGF signaling in endothelial cells, playing a role in angiogenesis, inflammation, and vascular permeability, which might be of potential interest for therapeutic applications.

show abstract

“…Additionally, it has been shown that there is an association between endocan level and vascular endothelial growth factor (VEGF) messenger ribonucleic acid in many studies. 15 It has been stated that endocan release is regulated by cytokines and growth factors such as VEGF in numerous studies. Moreover, in these studies, VEGF was found to induce endocan release through stimulation of endothelial migration and angiogenesis, which are induced by VEGF-A.…”

mentioning

confidence: 99%

Endocan Measurement for Active Behçet Disease

et al. 2017

View full text Add to dashboard Cite

Objectives: This study aims to investigate the relationships between serum endocan, vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-α) levels in active Behçet disease. Patients and methods: Forty patients with active Behçet disease (24 males, 16 females; mean age 37.6±8.7 years; range 20 to 50 years) and 40 healthy controls (22 males, 18 females; mean age 38.8±7.9 years; range 21 to 52 years) were included in this study. Both patient and control groups underwent a complete systemic and ophthalmic examination by the same specialist. Endocan, VEGF, and TNF-α levels were measured with an enzyme-linked immunosorbent assay kit in all subjects. Results: Serum endocan levels were 775.2±479.3 ng/mL and 275.8±145.8 ng/mL in the patient and control groups, respectively. VEGF levels were 1768.2±900.5 pg/mL and 980.2±135.3 pg/mL in the patient and control groups, respectively. TNF-α levels were 22.4±74.3 pg/mL-1 and 11.4±16.9 pg/mL-1 in the patient and control groups, respectively. There was a statistically significant difference between groups in terms of serum endocan, VEGF, and TNF-α levels. There was a significant positive correlation between serum endocan and VEGF levels in the patient group (r=0.630; p<0.001). Also, there was a significant positive correlation between serum endocan and TNF-α levels in the patient group (r=0.713; p<0.001). Conclusion: Serum endocan level may be a new marker in evaluation of both the prognosis and activity of Behçet disease.

show abstract

Endocan Is Upregulated on Tumor Vessels in Invasive Bladder Cancer Where It Mediates VEGF-A–Induced Angiogenesis

Cited by 158 publications

References 48 publications

Glycated serum albumin stimulates expression of endothelial cell specific molecule-1 in human umbilical vein endothelial cells: Implication in diabetes mediated endothelial dysfunction

Glycated serum albumin stimulates expression of endothelial cell specific molecule-1 in human umbilical vein endothelial cells: Implication in diabetes mediated endothelial dysfunction

Esm1 Modulates Endothelial Tip Cell Behavior and Vascular Permeability by Enhancing VEGF Bioavailability

Endocan Measurement for Active Behçet Disease

Contact Info

Product

Resources

About