Expression of <i>VE‐cadherin</i> in zebrafish embryos: A new tool to evaluate vascular development

Larson, Jon D.; Wadman, Shannon A.; Chen, Eleanor; Kerley, Lesa; Clark, Karl J.; Eide, Mark; Lippert, S; Nasevicius, Aidas; Ekker, Stephen C.; Hackett, Perry B.; Essner, Jeffrey J.

doi:10.1002/dvdy.20102

Cited by 94 publications

(96 citation statements)

References 31 publications

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“…For VE-cadherin riboprobe synthesis, we used the previously published plasmid (45). For Lgals1-L2 antisense-probe synthesis, RZPD clone IMAGp998D0710947Q3 (in pSPORT1) was linearized with BamHI and transcribed with T7 RNA polymerase.…”

Section: Methodsmentioning

confidence: 99%

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy

Thijssen¹,

Postel

Brandwijk³

et al. 2006

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

422

404

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We describe that galectin-1 (gal-1) is a receptor for the angiogenesis inhibitor anginex, and that the protein is crucial for tumor angiogenesis. gal-1 is overexpressed in endothelial cells of different human tumors. Expression knockdown in cultured endothelial cells inhibits cell proliferation and migration. The importance of gal-1 in angiogenesis is illustrated in the zebrafish model, where expression knockdown results in impaired vascular guidance and growth of dysfunctional vessels. The role of gal-1 in tumor angiogenesis is demonstrated in gal-1-null mice, in which tumor growth is markedly impaired because of insufficient tumor angiogenesis. Furthermore, tumor growth in gal-1-null mice no longer responds to antiangiogenesis treatment by anginex. Thus, gal-1 regulates tumor angiogenesis and is a target for angiostatic cancer therapy.angiostatic therapy ͉ endothelial cell ͉ galectin ͉ tumor models ͉ anginex A n adequate vasculature is a prerequisite for tumors to grow, and the need for neovessel formation (or angiogenesis) provides a target for treatment of cancer (1). Endothelial cells (EC) that line the tumor vasculature are particularly suitable target cells for therapeutic approaches, because they are easily accessible to agents delivered by the blood (2). However, to affect only tumor vasculature, specific targets on angiogenically active EC are essential. To date, only a few targets of tumor vasculature have been identified (3).We recently developed the specific angiostatic peptide anginex, which inhibits tumor growth through specific inhibition of angiogenesis (4-6). Although a broad profile of activities of anginex is known, such as prevention of EC adhesion and induction of apoptosis, the molecular target on tumor EC was never identified. In a receptor-finding study using a yeast twohybrid screening approach, we identified galectin-1 (gal-1) as a target protein of anginex.gal-1 belongs to a family of carbohydrate-binding proteins that share a conserved carbohydrate recognition domain of Ϸ130 aa (7-9). Over a dozen mammalian galectins have been described (10, 11), and members of this family are expressed in a wide range of species, suggesting an important role for galectins in basic cellular mechanisms. Galectins can be secreted and, depending on the cell type or state of differentiation, they have been found in the nucleus, cytoplasm, or extracellular matrix. It has been proposed that gal-1 mediates cell adhesion and migration (12) and is involved in several processes, including proliferation (13), apoptosis (14), and even mRNA splicing (15). The role of gal-1 in EC function or vascular biology has not been extensively studied.Here, we describe the function of gal-1 in angiogenesis. We provide direct functional evidence that gal-1 is required for tumor angiogenesis and outgrowth of tumors. Furthermore, we show that gal-1 is the target for the potent angiogenesis inhibitor anginex, thus establishing gal-1 as an important target for anticancer therapy.Results gal-1 Binds the Angiostatic Peptide Anginex...

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Section: Methodsmentioning

confidence: 99%

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy

Thijssen¹,

Postel

Brandwijk³

et al. 2006

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

422

404

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“…VE-cadherin is a cell-cell adhesion molecule that mediates endothelial cell survival, proliferation and vessel tube formation. In zebrafish, the VE-cadhern/Cdh5 gene is widely expressed in angioblasts and the developing vascular system and into adulthood (Larson et al, 2004). Strikingly, this group showed that morpholino knockdown of VE-cadherin expression selectively prevented tumor cell-induced angiogenesis by FGF2, but not normal vessel development including formation of the intersegmental and subintestinal vessels.…”

Section: Early Embryo Xenotransplantant Modelmentioning

confidence: 99%

Catch of the day: zebrafish as a human cancer model

2008

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Zebrafish are making big waves in the field of cancer research. The effect has been widespread and continues to gain speed as more and more cancer researchers ride the wave of zebrafish biology. This has been largely due to the development of transgenic and xenograft models of cancer, which recapitulate many aspects of different human cancers including lymphoblastic T-cell leukemia, pancreatic cancer, melanoma and rhabdomyosarcoma. These models are already being utilized by academia and industry to search for genetic and chemical modifiers of cancer with success. The attention has been further stimulated by the amenability of zebrafish to pharmacological testing and the superior imaging properties of fish tissues that allow visualization of cancer progression and angiogenesis in live animals. This review summarizes the current zebrafish models of cancer and discusses their utility in human cancer research and future directions in the field.

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“…In 54 hpf embryos, sprouts emanating from these primary lyve1-positive regions into the head, neck, and pharyngeal region expressed lyve1 (Fig. 2C,D), and at 80 hpf, these had spread and assumed a beaded appearance, quite distinct from expression of blood vessel markers (Thompson et al, 1998;Larson et al, 2004) (Fig. 2E,F).…”

Section: Zebrafish Lyve1 Marks Lymphangiogenesis Within the Whole Embryomentioning

confidence: 99%

“…An initial description of lyve1 expression within a 4-day post fertilization embryo has been previously reported (Hogan et al, 2009 (Srinivasan et al, 2007), and in zebrafish, thoracic duct lymphangioblasts bud from the posterior cardinal vein (Yaniv et al, 2006;Hogan et al, 2009). To determine whether lyve1-expressing cells derive from venous endothelia in zebrafish, lyve1 expression was compared with that of cadherin 5 (cdh5), a marker of blood vasculature (Larson et al, 2004). Double labeling with lyve1 and cdh5 riboprobes showed that these transcripts localized to the posterior cardinal vein at 26 hpf, but arterial endothelium and intersegmental vessels were devoid of lyve1 transcripts ( Fig.…”

Section: Zebrafish Lyve1 Marks Lymphangiogenesis Within the Whole Embryomentioning

confidence: 99%

Visualization of embryonic lymphangiogenesis advances the use of the zebrafish model for research in cancer and lymphatic pathologies

Flores

Hall

Crosier

et al. 2010

Developmental Dynamics

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Lymphangiogenesis induced during tumor growth contributes to metastasis. Genetic and chemical screens using the zebrafish model have the potential to enhance our understanding of lymphangiogenesis, and lead to the discovery of pharmacological agents with activity in the lymphatic system. Large-scale screening of lymphatic development in the whole zebrafish embryo requires a specific lymphatic endothelial cell marker. We isolated the zebrafish ortholog of Lyve1, and analyzed its expression pattern during embryogenesis, and under conditions where key regulators of lymphangiogenesis such as Prox1 and VegfC were depleted. Like humans, zebrafish embryos form lymph sacs, lymphangioblasts arise from venous endothelia, and they form asymmetric left and right collecting ducts. By monitoring the earliest lymphatic sprouting in the head, a pilot drug assay was performed showing rapamycin, an inhibitor of mammalian lymphangiogenesis, can also suppress zebrafish lymphangiogenesis. This work opens up a novel opportunity to further the understanding of, and potentially manipulate, human lymphangiogenesis. Developmental Dynamics 239:2128-2135,

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Expression of VE‐cadherin in zebrafish embryos: A new tool to evaluate vascular development

Cited by 94 publications

References 31 publications

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy

Catch of the day: zebrafish as a human cancer model

Visualization of embryonic lymphangiogenesis advances the use of the zebrafish model for research in cancer and lymphatic pathologies

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