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Neoangiogenesis during tail regeneration in Xenopus
14th IVBM Abstracts
Tumor Biology and Angiogenesis, Genentech Inc., South San Francisco, United States of America EGFL7 is a vascular specific gene that is expressed during embryonic development. Expression is down regulated in the quiescent vasculatures in the adult, but is reactivated in adult tissues that require new blood vessel growth or remodeling, such as the pregnant uterus, wounds or tumors. We found that EGFL7 protein is secreted from the endothelial cells and is integrated into the extracellular matrix (ECM) around nascent blood vessels, and it forms a complex with other ECM components such as Fibronectin. We used loss of function approaches to analyze the role of EGFL7 protein during the formation and remodeling of the vascular network, and discovered that EGFL7 is required for neovascularization in tumors and organ growth.
e127
characterize the expression profile of genes known to be important during vascular development during regeneration of the tail in Xenopus. We next plan to initiate a functional analysis of these genes to determine which genes are involved in the regeneration of the vasculature in the tail. doi:10.1016/j.vph.2006.08.337
B16.36 Withdrawn doi:10.1016/j.vph.2006.08.338
B16.37 doi:10.1016/j.vph.2006.08.336
Expression of LYVE-1 by stabilin-1+, F4/80+, CD11B+ macrophages in malignant tumours and wound healing tissue indicates a contribution of endothelial-like macrophages to lymphatic vessels during lymphangiogenesis
B16.35 Neoangiogenesis during tail regeneration in Xenopus 1
Nicholas Love , Enrique Amaya
2
Kai Schledzewski1, Martin Falkowski1, Pat Metharom1, Julia Kzhyshkowska1, Alexandra Demory1, Diana Klein1, Bernd Arnold2, Sergij Goerdt1
1
Gurdon Institute-University of Cambridge, Cambridge, United Kingdom 2 Healing Foundation Centre-University of Manchester, Manchester, United Kingdom The ability to regenerate lost parts is a fairly common feature within the animal and plant kingdoms. Some vertebrates, such as amphibians, possess particularly striking capacities to regenerate lost body parts following injury. For example, salamanders are able to regenerate their limbs, tails, jaws, retina, lens and even sections of their heart following loss or injury. Frog tadpoles are also able to regenerate lost tails and limbs. During tail regeneration, the many different tissue types that make up a functional tail, such as muscles, neurons, notochord and fin epidermis, must reform in the correct pattern. In addition, the tail must regenerate its vasculature, including both the cardinal veins and aorta. While some effort has been made recently to understand the molecular mechanism responsible for tail regeneration in the frog, Xenopus, no study yet has been described focusing on the regeneration of the vasculature in this system. Xenopus has great potential as a novel system to study the molecular basis of neoangiogenesis. Firstly tadpoles can be produced in large numbers, thus there is an almost limitless amount of experimental material to study. Secondly, large-scale genomic efforts in Xenopus tropicalis have resulted in more than 1 million ESTs, as well as the sequencing of its genome, thus providing us with essentially all the genes likely to be involved in neoangiogenesis. Thirdly, gain and loss of function experiments can be easily performed in this system through the use of transgenesis and electroporation of antisense morpholino oligonucleotides, respectively. As a first step we have begun to
1
Dermatology-University Medical Centre-University Heidelberg, Mannheim, Germany 2 Department of Molecular Immunology-DKFZ, Heidelberg, Germany Lymphangiogenesis is a novel prognostic parameter for several cancers that is preferentially quantified by immunohistochemistry of the lymphatic endothelium-specific hyaluronan receptor LYVE-1. Recently, the specificity of LYVE-1 was challenged by serendipitous observations of LYVE-1 expression in rare tissue macrophages. As the hyaluronan receptor-like molecule stabilin-1 is shared by sinusoidal endothelium and macrophages, we performed a thorough analysis of LYVE-1 expression using macrophage-specific markers in vivo and in vitro. In murine tumour models and excisional wound healing, LYVE-1 expression occurred in a subset of CD11b+, F4/80+ tissue macrophages that preferentially co-expressed stabilin-1. Upon comparison of single and double labelling immunofluorescence, it became apparent that LYVE-1+ macrophages mimic sprouting and collapsed lymphatic vessels. In vitro, LYVE-1 expression was induced in 25–40% of murine bone marrow-derived macrophages upon exposure to B16F1 melanoma-conditioned medium and IL-4/dexamethasone. Upon FACS analysis, 11.5% of bone marrow-derived macrophages were LYVE-1+, stabilin-1+ double positive, while 9.9% were LYVE-1+, stabilin-1- and 33.5% were LYVE-1-, stabilin-1+. Northern and Western analyses confirmed expression of LYVE1 mRNA and protein in bone marrow-derived macrophages. In light of the current debate about true endothelial transdifferentiation versus endothelial mimicry of monocytes/
Tumor Biology and Angiogenesis, Genentech Inc., South San Francisco, United States of America EGFL7 is a vascular specific gene that is expressed during embryonic development. Expression is down regulated in the quiescent vasculatures in the adult, but is reactivated in adult tissues that require new blood vessel growth or remodeling, such as the pregnant uterus, wounds or tumors. We found that EGFL7 protein is secreted from the endothelial cells and is integrated into the extracellular matrix (ECM) around nascent blood vessels, and it forms a complex with other ECM components such as Fibronectin. We used loss of function approaches to analyze the role of EGFL7 protein during the formation and remodeling of the vascular network, and discovered that EGFL7 is required for neovascularization in tumors and organ growth.
e127
characterize the expression profile of genes known to be important during vascular development during regeneration of the tail in Xenopus. We next plan to initiate a functional analysis of these genes to determine which genes are involved in the regeneration of the vasculature in the tail. doi:10.1016/j.vph.2006.08.337
B16.36 Withdrawn doi:10.1016/j.vph.2006.08.338
B16.37 doi:10.1016/j.vph.2006.08.336
Expression of LYVE-1 by stabilin-1+, F4/80+, CD11B+ macrophages in malignant tumours and wound healing tissue indicates a contribution of endothelial-like macrophages to lymphatic vessels during lymphangiogenesis
B16.35 Neoangiogenesis during tail regeneration in Xenopus 1
Nicholas Love , Enrique Amaya
2
Kai Schledzewski1, Martin Falkowski1, Pat Metharom1, Julia Kzhyshkowska1, Alexandra Demory1, Diana Klein1, Bernd Arnold2, Sergij Goerdt1
1
Gurdon Institute-University of Cambridge, Cambridge, United Kingdom 2 Healing Foundation Centre-University of Manchester, Manchester, United Kingdom The ability to regenerate lost parts is a fairly common feature within the animal and plant kingdoms. Some vertebrates, such as amphibians, possess particularly striking capacities to regenerate lost body parts following injury. For example, salamanders are able to regenerate their limbs, tails, jaws, retina, lens and even sections of their heart following loss or injury. Frog tadpoles are also able to regenerate lost tails and limbs. During tail regeneration, the many different tissue types that make up a functional tail, such as muscles, neurons, notochord and fin epidermis, must reform in the correct pattern. In addition, the tail must regenerate its vasculature, including both the cardinal veins and aorta. While some effort has been made recently to understand the molecular mechanism responsible for tail regeneration in the frog, Xenopus, no study yet has been described focusing on the regeneration of the vasculature in this system. Xenopus has great potential as a novel system to study the molecular basis of neoangiogenesis. Firstly tadpoles can be produced in large numbers, thus there is an almost limitless amount of experimental material to study. Secondly, large-scale genomic efforts in Xenopus tropicalis have resulted in more than 1 million ESTs, as well as the sequencing of its genome, thus providing us with essentially all the genes likely to be involved in neoangiogenesis. Thirdly, gain and loss of function experiments can be easily performed in this system through the use of transgenesis and electroporation of antisense morpholino oligonucleotides, respectively. As a first step we have begun to
1
Dermatology-University Medical Centre-University Heidelberg, Mannheim, Germany 2 Department of Molecular Immunology-DKFZ, Heidelberg, Germany Lymphangiogenesis is a novel prognostic parameter for several cancers that is preferentially quantified by immunohistochemistry of the lymphatic endothelium-specific hyaluronan receptor LYVE-1. Recently, the specificity of LYVE-1 was challenged by serendipitous observations of LYVE-1 expression in rare tissue macrophages. As the hyaluronan receptor-like molecule stabilin-1 is shared by sinusoidal endothelium and macrophages, we performed a thorough analysis of LYVE-1 expression using macrophage-specific markers in vivo and in vitro. In murine tumour models and excisional wound healing, LYVE-1 expression occurred in a subset of CD11b+, F4/80+ tissue macrophages that preferentially co-expressed stabilin-1. Upon comparison of single and double labelling immunofluorescence, it became apparent that LYVE-1+ macrophages mimic sprouting and collapsed lymphatic vessels. In vitro, LYVE-1 expression was induced in 25–40% of murine bone marrow-derived macrophages upon exposure to B16F1 melanoma-conditioned medium and IL-4/dexamethasone. Upon FACS analysis, 11.5% of bone marrow-derived macrophages were LYVE-1+, stabilin-1+ double positive, while 9.9% were LYVE-1+, stabilin-1- and 33.5% were LYVE-1-, stabilin-1+. Northern and Western analyses confirmed expression of LYVE1 mRNA and protein in bone marrow-derived macrophages. In light of the current debate about true endothelial transdifferentiation versus endothelial mimicry of monocytes/