Recent Advances in Angiogenesis and ... - Bentham Science

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v Vito Pistoia Head, Laboratory of Oncology, G. Gaslini Children’s Hospital, Genoa, Italy Mirco Ponzoni Head, Experimental Therapies Unit, Laboratory of Oncology,“G. Gaslini” Children’s Hospital, Genoa, Italy Marco Presta Full professor, Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia Medical School, Brescia, Italy Lizzia Raffaghello Fellow, Fondazione Italiana per la Lotta al Neuroblastoma, “G. Gaslini” Children’s Hospital Genoa, Italy Marius Raica Full Professor, Department of Histology and Molecular Pathology, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania Roberto Ria Assistant Research, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy Domenico Ribatti Full Professor, Department of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy Aldo M. Roccaro Instructor in Medicine, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA Guido Serini Assistant Researcher, Insitute for Cancer Research and Treatment , and Department of Oncological Sciences, University of Torino Medical School, Candiolo, Italy Yuval Shaked Assistant Professor, Technion Israel Institute of Technology,and Department of Molecular Pharmacology, Rappaport Faculty of Medicine, Haifa, Israel Giulia Taraboletti Head, Tumor Angiogenesis Unit, Department of Oncology, Mario Negri Institute for Pharmacological Research, Bergamo, Italy Gillian M. Tozer Full Professor, Tumour Microcirculation Group, Section of Oncology, School of Medicine & Biomedical Sciences, University of Sheffield, Sheffield, UK Gerold Untergasser Assistant Professor, Tumor Biology & Angiogenesis Laboratory, Department of Internal Medicine V, Universty of Innsbruck Medical School, Innsbruck, Austria Angelo Vacca Full Professor, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy Donatella Valdembri .Fellow, Insitute for Cancer Research and Treatment , and Department of Oncological Sciences, University of Torino Medical School, Candiolo, Italy
Recent Advances in Angiogenesis and Antiangiogenesis, 2009, 1-9 1 CHAPTER 1 Plexins and Neuropilins Regulate Integrin Conformation and Trafficking in Endothelial Cells Guido Serini, Donatella Valdembri and Federico Bussolino Institute for Cancer Research and Treatment, and Department of Oncological Sciences, University of Torino, I- 10060 Candiolo, Italy Address correspondence to: Dr. Federico Bussolino, Institute for Cancer Research and Treatment- Strada provinciale di Piobesi 142, Km 3.95 10060 Candiolo, Italy; Tel: 0039 011 9933347; Fax: 0039 011 9933524; E-mail: federico.bussolino@ircc.it 1. INTRODUCTION Abstract: Integrin the are major extracellular matrix receptors and their functional state with respect to the affinity for extracellular matrix proteins is pivotal for their biological activities in physiologic and pathological settings. Integrins’ machinery depends on the dynamic regulation of their adhesive function in space and time. In cells, integrins exist in different conformations which determine their affinity for extracellular matrix proteins and are continuously endocytosed, trafficked through endosomal compartments, and recycled back to the plasma membrane. Therefore real-time modulation of cell - extracellular matrix adhesion can result from two interconnected phenomena: the regulation of integrin conformation and traffic in response to extracellular stimuli. This review summarizes recent data highlighting the different mechanisms by which semaphorins and their receptors plexins and neuropilins regulate integrin functions in vascular system. Cell adhesion to the extracellular matrix (ECM) is mainly mediated by integrins, a protein family that signs the evolution from protozans to metazoans. A functional integrin is composed of non-homologous transmembrane and subunits that control cell adhesion through complex molecular mechanisms. Outside-in signaling informs the cell about the ECM environment, while inside-out signaling promotes modifications in integrin functional activity [1, 2]. In the last 10 years, an increasing body of evidences has demonstrated that integrins are not mere adhesion receptors, but interact and influence the biological activity of several other molecular systems within the cell [3]. Vascular system represents an outstanding example to understand how the dynamic interactiona between cells and ECM influence tissue behaviors both in physiologic and pathological conditions. Vascular cells (i.e. endothelium, pericytes and smooth muscle cells) express a wide range of integrins including 11, 21, 41, 51, v1, v3, v5, v8, 61 and 64 [4]. During angiogenic remodeling of pre-existing vessels, endothelial cells (ECs) move and change their reciprocal positions and interactions in Domenico Ribatti (Ed.) All rights reserved - © 2009 Bentham Science Publishers Ltd. response to the several guidance cues that control their motility. As a result of a balanced response to fluid shear stress, chemoattractant and chemorepulsive agents, ECs dynamically regulate their adhesiveness both in terms of cell-to-cell and cell-to- ECM contacts. Integrin-mediated cell-to-ECM adhesion play a deterministic role in vascular development by contributing to cell movement, to protect cells from anoikis and to endow the vasculature with the ability to sense and respond to changes in physical forces [4, 5]. The mechanisms regulating the interactions between cells and ECM are mainly based on the specific ECM composition that characterizes organs and tissues [6], on diverse integrin conformational states endowed with different binding affinity for ECM proteins [1, 2] and on integrin membrane trafficking [7]. Many elegant experiments have explained the molecular mechanisms supporting integrin activation by growth factors, chemokines and shear stress [1, 2]. On the contrary the molecular events switching-off activated integrins are under extensive investigation. Recent evidences strongly indicate that semaphorins (Sema) and their receptors plexins (Plx) and neuropilins (Nrp) play a determinant role in counterbalancing the growth factor activity on integrin functional state.
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Page 4 and 5: FOREWORD It has been known for a ve
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