HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium

Abstract

Background:Tumour stromal cells differ from its normal counterpart. We have shown that tumour endothelial cells (TECs) isolated from tumour tissues are also abnormal. Furthermore, we found that mRNAs of vascular endothelial growth factor-A (VEGF-A) and cyclooxygenase-2 (COX-2) were upregulated in TECs. Vascular endothelial growth factor-A and COX-2 are angiogenic factors and their mRNAs contain an AU-rich element (ARE). AU-rich element-containing mRNAs are reportedly stabilised by Hu antigen R (HuR), which is exported to the cytoplasm.Methods:Normal endothelial cell (NEC) and two types of TECs were isolated. We evaluated the correlation of HuR and accumulation of VEGF-A and COX-2 mRNAs in TECs and effects of HuR on biological phenotypes of TECs.Results:The HuR protein was accumulated in the cytoplasm of TECs, but not in NECs. Vascular endothelial growth factor-A and COX-2 mRNA levels decreased due to HuR knockdown and it was shown that these ARE-mRNA were bound to HuR in TECs. Furthermore, HuR knockdown inhibited cell survival, random motility, tube formation, and Akt phosphorylation in TECs.Conclusion:Hu antigen R is associated with the upregulation of VEGF-A and COX-2 mRNA in TECs, and has an important role in keeping an angiogenic switch on, through activating angiogenic phenotype in tumour endothelium.

High Consumption of Green Tea Suppresses Urinary Tract Recurrence of Urothelial Cancer via Down-regulation of Human Antigen-R Expression in Never Smokers

“…HuR is involved in posttranscriptional regulation of RNA turnover and stability (25). molecules including vascular endothelial growth factors, cyclooxygenase, and matrix metalloproteins via stability of their mRNA (26)(27)(28)(29). These HuR-related molecules play important roles in carcinogenesis, cancer cell proliferation, angiogenesis, and tumor invasion in UC (30)(31)(32)(33).…”

Size-controlled, dual-ligand modified liposomes that target the tumor vasculature show promise for use in drug-resistant cancer therapy

“…TECs from OS-RC-2 tumor tissue were successfully collected, as described previously [17][18][19][20][21][22]. As shown in Fig.…”

“…TECs were isolated, as described previously [17][18][19][20][21][22]. In a typical procedure, the TECs were isolated from OS-RC-2 tumors and dermal tissue in tumor-bearing mice using a magnetic cell sorting system (MACS; Milteny Biotec, Tokyo, Japan).…”

Inhibition of Multidrug Transporter in Tumor Endothelial Cells Enhances Antiangiogenic Effects of Low-Dose Metronomic Paclitaxel

“…Frozen sections of excised tissues were prepared as described elsewhere. 26 To assess P-gp co-localization in tumor blood vessels, frozen sections were double stained with rat anti-mouse CD31eAlexa Fluor 647 and rabbit anti-MDR1/P-gp antibodies, followed by counterstaining with DAPI to stain nuclei. To detect apoptotic ECs, frozen sections were double stained with rat anti-mouse CD31eAlexa Fluor 647 and antiecleaved caspase 3 antibodies.…”