caa a22 4500 606176780 CHVBK 20210128100749.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00018-014-1814-x doi (NATIONALLICENCE)springer-10.1007/s00018-014-1814-x Lipid rafts: integrated platforms for vascular organization offering therapeutic opportunities [Elektronische Daten] [Anna Laurenzana, Gabriella Fibbi, Anastasia Chillà, Giancarlo Margheri, Tommaso Del Rosso, Elisabetta Rovida, Mario Del Rosso, Francesca Margheri] Research on the nanoscale membrane structures known as lipid rafts is relevant to the fields of cancer biology, inflammation and ischaemia. Lipid rafts recruit molecules critical to signalling and regulation of the invasion process in malignant cells, the leukocytes that provide immunity in inflammation and the endothelial cells that build blood and lymphatic vessels, as well as the patterning of neural networks. As angiogenesis is a common denominator, regulation of receptors and signalling molecules critical to angiogenesis is central to the design of new approaches aimed at reducing, promoting or normalizing the angiogenic process. The goal of this review is to highlight some of the key issues that indicate the involvement of endothelial cell lipid rafts at each step of so-called ‘sprouting angiogenesis', from stimulation of the vascular endothelial growth factor to the choice of tip cells, activation of migratory and invasion pathways, recruitment of molecules that guide axons in vascular patterning and maturation of blood vessels. Finally, the review addresses opportunities for future studies to define how these lipid domains (and their constituents) may be manipulated to stimulate the so-called ‘normalization' of vascular networks within tumors, and be identified as the main target, enabling the development of more efficient chemotherapeutics and cancer immunotherapies. Springer Basel, 2014 Endothelial cell nationallicence Angiogenesis nationallicence Vascular guidance nationallicence Vessel maturation nationallicence Vessel normalization nationallicence Caveolin nationallicence Tip cell nationallicence ECs : Endothelial cells nationallicence EPCs : Endothelial progenitor cells nationallicence ECM : Extracellular matrix nationallicence VEGF : Vascular endothelial growth factor nationallicence LRs : Lipid rafts nationallicence GPI : Glycosylphosphatidylinositol nationallicence ssBLMs : Solid-supported bilayer lipid membranes nationallicence Cav-1 : Caveolin-1 nationallicence Cav : Caveolin nationallicence PTRF : Polymerase I and transcript release factor nationallicence VEGFR2 : Vascular endothelial growth factor receptor 2 nationallicence KDR : Kinase insert domain receptor nationallicence FLK1 : Fetal liver kinase 1 nationallicence VEGFR1/Flt1 : Vascular endothelial growth factor receptor 1/fms-related tyrosine kinase 1 nationallicence Prxs : Peroxirederoxins nationallicence ROS : Reactive oxygen species nationallicence MMP : Metalloprotease nationallicence TACE : Tumor necrosis alpha converting enzyme nationallicence MMPs : Matrix metalloproteinases nationallicence uPAR : Urokinase-type-plasminogen activator receptor nationallicence MT1-MMP : Membrane-type-1-MMP nationallicence DEP1 : Density-enhanced tyrosine phosphatase nationallicence ERK1/2 : Extracellular signal-regulated kinase 1/2 nationallicence Robos : Roundabouts nationallicence UNC5B : Unc-5 homolog B nationallicence Nrps : Neuropilins nationallicence Slit1-3 : Slit homolog 1-3 nationallicence RGMa : Repulsive guidance molecule a nationallicence FLRT3 : Fibronectin and leucine rich transmembrane protein 3 nationallicence Semas : Semaphorins nationallicence vSMC : Vascular smooth muscle cell nationallicence PDGFRβ : Platelet-derived growth factor receptor β nationallicence S1P : Sphingosine-1-phosphate nationallicence TGF β1 : Transforming growth factor-β1 (TGFβ1) nationallicence ALK1 : Activin receptor-like kinase 1 nationallicence ALK5 : Activin receptor-like kinase 5 nationallicence TIE2 : TEK tyrosine kinase nationallicence Ang : Angiopoietin nationallicence n-3 PUFA : n-3 polyunsaturated fatty acids nationallicence Laurenzana Anna Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy aut Fibbi Gabriella Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy aut Chillà Anastasia Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy aut Margheri Giancarlo Institute of Complex Systems (ISC), Consiglio Nazionale delle Ricerche (CNR), Florence, Italy aut Del Rosso Tommaso Department of Physics, Pontificia Universidade Catolica do Rio de Janeiro, Rio de Janeiro, Brazil aut Rovida Elisabetta Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy aut Del Rosso Mario Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy aut Margheri Francesca Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy aut Cellular and Molecular Life Sciences Springer Basel 72/8(2015-04-01), 1537-1557 1420-682X 72:8<1537 2015 72 18 https://doi.org/10.1007/s00018-014-1814-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1814-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Laurenzana Anna Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy aut NATIONALLICENCE 700 1- Fibbi Gabriella Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy aut NATIONALLICENCE 700 1- Chillà Anastasia Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy aut NATIONALLICENCE 700 1- Margheri Giancarlo Institute of Complex Systems (ISC), Consiglio Nazionale delle Ricerche (CNR), Florence, Italy aut NATIONALLICENCE 700 1- Del Rosso Tommaso Department of Physics, Pontificia Universidade Catolica do Rio de Janeiro, Rio de Janeiro, Brazil aut NATIONALLICENCE 700 1- Rovida Elisabetta Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy aut NATIONALLICENCE 700 1- Del Rosso Mario Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy aut NATIONALLICENCE 700 1- Margheri Francesca Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/8(2015-04-01), 1537-1557 1420-682X 72:8<1537 2015 72 18