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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.

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The polyphenol epigallocatechin-3 gallate (EGCG) in green tea suppresses tumor growth by direct action on tumor cells and by inhibition of angiogenesis, but it is not known whether it specifically inhibits tumor angiogenesis. We examined the antiangiogenic effect of EGCG on tumor-associated endothelial cells (TEC), endothelial progenitor cells (EPC), and normal endothelial cells (NEC). EGCG suppressed the migration of TEC and EPC but not NEC. EGCG also inhibited the phosphorylation of Akt in TEC but not in NEC. Furthermore, vascular endothelial growth factor-induced mobilization of EPC into circulation was inhibited by EGCG. MMP-9 in the bone marrow plasma plays key roles in EPC mobilization into circulation. We observed that expression of MMP-9 mRNA was downregulated by EGCG in mouse bone marrow stromal cells. In an in vivo model, EGCG suppressed growth of melanoma and reduced microvessel density. Our study showed that EGCG has selective antiangiogenic effects on TEC and EPC. It is suggested that EGCG could be a promising angiogenesis inhibitor for cancer therapy. T ea is one of the most popular beverages consumed worldwide. Drinking tea, especially green tea, inhibits the growth of several tumors in animal models, including cancers of the skin, lung, esophagus, breast, stomach, small intestine, colon, liver, pancreas, and mammary glands, (1,2) and is associated with a lower incidence of cancer in humans.(1,3,4) The components of green tea responsible for these effects are catechins, which are polyphenols with potent antioxidant capacity that have been shown to inhibit mutation, tumor cell growth, tumor initiation, tumor progression, and the activity of urokinase and MMP, which are crucial for cancer growth.(5-7) Among these catechins, epigallocatechin-3 gallate (EGCG) has the highest antioxidant capacity and is an effective inhibitor of corneal vascularization in vivo. (8) The tumor microenvironment has recently been regarded as a target of cancer chemoprevention because it plays an important role in tumorigenesis and tumor progression.(9) Tumor angiogenesis is one of the key processes within the tumor microenvironment, and controlling this process is a very important strategy for preventing invasive cancers.(10) Many molecules regulating tumor angiogenesis have been identified and characterized recently, including vascular endothelial growth factor (VEGF). (11,12) EGCG has also been shown to inhibit cell proliferation, (13) binding of VEGF to its receptors, (14) phosphorylation of VEGF receptor (VEGFR) 2, (15) MMP activity, (13) and interleukin-8 production (16) in normal endothelial cells such as human umbilical vein endothelial cells.An important concept in tumor angiogenesis is that tumor blood vessels contain endothelial cells that are genetically normal and stable, whereas tumor cells are typically genetically unstable.(17) However, tumor vessels and tumor-associated endothelial cells (TEC) differ from their normal counterparts in many respects. (18)(19)(20) Tumor vessels show structural changes such as ...