Transcriptional profiling of VEGF-A and VEGF-C target genes in lymphatic endothelium reveals endothelial-specific molecule-1 as a novel mediator of lymphangiogenesis

Shin, Jay W.; Huggenberger, Reto; Detmar, Michael

doi:10.1182/blood-2008-05-156331

Cited by 133 publications

(141 citation statements)

References 71 publications

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“…VEGF-C deals with growth of blood vessels and lymphatics (26). VEGF-A and C binds with a high affi nity to two related receptor tyrosine kinases expressed on vascular endothelial cells (27).…”

Section: Discussionmentioning

confidence: 99%

Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage

Bagheri¹,

Kumar²,

Kamath³

et al. 2017

BLL

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INTRODUCTION: Recurrent miscarriage (RM) defi ned as 2 or more spontaneous miscarriage before 20 weeks of gestation, affects at least 1 % of couples trying to conceive. In over 50 % of cases, the cause of the loss of pregnancy remains unexplained. Reduced expression of Angiogenic factors such as: vascular endothelial growth factor (VEGF-A) and VEGF-C has been linked with spontaneous miscarriage, likely due to defective foetal and placental angiogenesis. AIMS AND OBJECTIVES: To investigate the relationships between serum level of VEGF-A and VEGF-C with clinical characteristic in women with URM and compare to pregnant and healthy women. MATERIALS AND METHODS: A case-control study, which was conducted between 90 non-pregnant women with history of RM, age-matched with 70 non-pregnant women without history of recurrent abortion with at least one child (controls) and 70 pregnant women without history of recurrent abortion with at least one child (controls). Those with unexplained RM were eligible. Demographic and Anthropometric data were retrieved by pre-test questionnaire and serum level of VEGF-A and VEGF-C measured by ELISA kit. RESULTS: This study showeds that maternal levels of VEGF-A and VEGF-C were distinctly lower in RSA (189.87±88.1 vs 238.8±99.6) compared to healthy (239.1±99.7 vs 275.5±133.08) and pregnant (301.5±76.4 vs 402.5±128.6) women as control groups. Univariate analysis demonstrated that clinical characteristic factors were signifi cantly associated with concentration of VEGF-A and VEGF-C in cases and controls. CONCLUSIONS: Our fi ndings suggest that these molecules could be used as potential predictive markers of miscarriage in these women presenting with URM (Tab. 4, Fig. 5, Ref. 40). Text in PDF www.elis.sk.

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Section: Discussionmentioning

confidence: 99%

Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage

Bagheri¹,

Kumar²,

Kamath³

et al. 2017

BLL

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“…Endocan is a secreted proteoglycan (12) that is upregulated by growth factors and chemokines in vitro (13,14) and on tumor vasculature in several types of cancer (15)(16)(17), with diverse suggested biologic roles (18). Using quantitative reverse-transcription PCR (qRT-PCR) and immunohistochemistry, we found that endocan was strongly upregulated on tumor vascular endothelium and that its expression correlated with the invasiveness of bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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Tumor-associated blood vessels differ from normal vessels and proteins present only on tumor vessels may serve as biomarkers or targets for antiangiogenic therapy in cancer. Comparing the transcriptional profiles of blood vascular endothelium from human invasive bladder cancer with normal bladder tissue, we found that the endothelial cell-specific molecule endocan (ESM1) was highly elevated on tumor vessels. Endocan was associated with filopodia of angiogenic endothelial tip cells in invasive bladder cancer. Notably, endocan expression on tumor vessels correlated strongly with staging and invasiveness, predicting a shorter recurrence-free survival time in noninvasive bladder cancers. Both endocan and VEGF-A levels were higher in plasma of patients with invasive bladder cancer than healthy individuals. Mechanistic investigations in cultured blood vascular endothelial cells or transgenic mice revealed that endocan expression was stimulated by VEGF-A through the phosphorylation and activation of VEGFR-2, which was required to promote cell migration and tube formation by VEGF-A. Taken together, our findings suggest that disrupting endocan interaction with VEGFR-2 or VEGF-A could offer a novel rational strategy to inhibit tumor angiogenesis. Furthermore, they suggest that endocan might serve as a useful biomarker to monitor disease progression and the efficacy of VEGF-A–targeting therapies in patients with bladder cancer. Cancer Res; 73(3); 1097–106. ©2012 AACR.

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“…Therefore, we next investigated whether HMGCR was expressed in LECs in our recently published LEC microarray data. We found that HMGCR is expressed in human dermal microvascular LECs that were used for this study (13) and also in murine intestinal LECs (14). Mevalonate, the product of HMGCR, and its derivatives farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) build the basis for cholesterol synthesis.…”

Section: Identification Of Lymphangiogenic Sprouting Inhibitors By Lomentioning

confidence: 99%

Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis

Schulz

Reisen

Zgraggen

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Lymphangiogenesis plays an important role in promoting cancer metastasis to sentinel lymph nodes and beyond and also promotes organ transplant rejection. We used human lymphatic endothelial cells to establish a reliable three-dimensional lymphangiogenic sprouting assay with automated image acquisition and analysis for inhibitor screening. This high-content phenotype-based assay quantifies sprouts by automated fluorescence microscopy and newly developed analysis software. We identified signaling pathways involved in lymphangiogenic sprouting by screening the Library of Pharmacologically Active Compounds ðLOPACÞ 1280 collection of pharmacologically relevant compounds. Hit characterization revealed that mitogen-activated protein kinase kinase (MEK) 1/2 inhibitors substantially block lymphangiogenesis in vitro and in vivo. Importantly, the drug class of statins, for the first time, emerged as potent inhibitors of lymphangiogenic sprouting in vitro and of corneal and cutaneous lymphangiogenesis in vivo. This effect was mediated by inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and subsequently the isoprenylation of Rac1. Supplementation with the enzymatic products of HMG-CoA reductase functionally rescued lymphangiogenic sprouting and the recruitment of Rac1 to the plasma membrane.high-content screening | small compound screening | lymphatic endothelium | chemical genetics

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Transcriptional profiling of VEGF-A and VEGF-C target genes in lymphatic endothelium reveals endothelial-specific molecule-1 as a novel mediator of lymphangiogenesis

Cited by 133 publications

References 71 publications

Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage

Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage

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

Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis

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