The Role of Microenvironment in the Control of Tumor Angiogenesis

The Role of Microenvironment in the Control of Tumor Angiogenesis

Domenico Ribatti The Role of Microenvironment in the Control of Tumor Angiogenesis

Domenico Ribatti Department of Basic Medical Sciences, Neurosciences and Sensory Organs University of Bari Medical School Bari, Italy National Cancer Institute Giovanni Paolo II Bari, Italy ISBN 978-3-319-27818-6 DOI 10.1007/978-3-319-27820-9 ISBN 978-3-319-27820-9 (ebook) Library of Congress Control Number: 2016930402 Springer International Publishing Switzerland 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper This Springer imprint is published by SpringerNature The registered company is Springer International Publishing AG Switzerland

Acknowledgments This work was supported by European Union Seventh Framework Programme (FPT7/2007 2013) under grant agreement n 278570 to DR. v

Contents 1 Tumor Microenvironment... 1 1 Metastatic Cascade... 5 2 Epithelial-Mesenchymal Transition... 8 3 The Extracellular Matrix... 9 2 Tumor Blood Vessels and Tumor Endothelial Cells... 11 1 Tumor Basement Membrane... 14 2 Tumor Pericytes... 15 3 Tumor Angiogenesis... 19 1 Sprouting Angiogenesis... 20 2 Vascular Co-option... 20 3 Vasculogenic Mimicry... 21 4 Intussusceptive Microvascular Growth... 22 4 Inflammatory Cells in Tumor Microenvironment... 27 1 Neutrophils... 31 2 Eosinophils and Dendritic Cells... 31 3 Lymphocytes and Platelets... 32 4 Mast Cells... 33 5 Macrophages... 36 6 Tie-2 Expressing Monocytes (TEMs)... 39 7 Fibroblasts... 40 8 Osteoblasts and Osteoclasts... 41 9 Cancer Stem Cells (CSCs)... 42 10 Circulating Endothelial Cells and Endothelial Precursor Cells... 46 11 Multipotent Adult Progenitor Cells (MAPCs) and Myeloid-Derived Suppressor Cells (MDSCs)... 49 vii

viii Contents 5 Therapeutic Strategies, the Concept of Normalization and the Role of VEGF Inhibition... 51 References... 61 Index... 85

List of Abbreviations ALDH1 Aldehyde dehydrogenase 1 AML Acute myeloid leukemia ANG-1 Angiopoietin-1 APL Acute promyelocytic leukemia A-SMA Alpha smooth actin ATRA All trans retinoic acid BM Bone marrow BMP Bone morphogenetic protein CAM Chorioallantoic membrane CCL5 Chemokine (C-C motif) ligand-5 COX-2 Cycloxygenase-2 CSC Cancer stem cell CSF Colony stimulating factor CSF-1R CSF-1 receptor CXCL Chemokine (C-X-C motif) ligand DLBCL Diffuse large B-cell lymphoma ECs Endothelial cells ECM Extracellular matrix EDG-1 Endothelial differentiation gene-1 EGF Epidermal growth factor EMT Epithelial mesenchymal transition enos Endothelial nitric oxide synthase EPCs Endothelial precursor or progenitor cells ESA Epidermal surface antigen FAP Fibroblast activating protein FDA Food and Drug Administration FGF-2 Fibroblast growth factor-2 FSP-1 Fibroblast specific protein-1 GCSF Granulocyte colony stimulating factor GFP Green fluorescent protein ix

x GIST GM-CSF GSC HCs HGF HIFs HPCs HPV HRG HSCs ICAM IFN IGF-1 IL IMG inos LT-CSC M-CSF mtor MAPCs MCP MDSCs MET MGUS MIP-2 MM MMP-9 MSCs MT1-MMP mtor NAID NECA NG2 NGF NK NOD-SCID NSAIDs NSCLS OPN PlGF-1 PA PAR PC PDGF PDGFR List of Abbreviations Gastrointestinal stroma tumors Granulocyte macrophage colony stimulating factor Glioblastoma stem-like cells Hematopoietic Cells Hepatocyte growth factor Hypoxia inducible factors Hematopoietic precursor cells Human papilloma virus Histidine-rich glycoprotein Hematopoietic stem cells Intercellular cellular adhesion molecule Interferon Insulin-like growth factor-1 Interleukin Intussusceptive microvascular growth Inducible nitric oxide synthase Long term CSC Macrophage-colony stimulating factor Mammalian target of rapamycin Multipotent adult progenitor cells Monocyte chemotactic protein Myeloid derived suppressor cells Mesenchymal epithelial transition Monoclonal gammopathy of undetermined significance Macrophage inflammatory protein-2 Multiple myeloma Matrix metalloproteinase-9 Mesenchymal stem cells Membrane type-1-mmp Mammalian target of rapamycin Nonsteroidal anti-inflammatory drugs N-methyl carboxamide adenosine Nerve/glial antigen-2 Nerve growth factor Natural killer Non obese diabetic/severe combined immunodeficiency Non-steroidal anti-inflammatory drugs Non small cell lung cancer Osteopontin Placental growth factor-1 Plasminogen activator Protease activated receptor Pericytes Platelet derived growth factor Platelet derived growth factor receptor

List of Abbreviations xi PGE2 Prostaglandin E2 PSMA Prostate specific membrane antigen PTX-3 Pantraxin-3 PyMT Polyoma middle-t RA Retinoic acid RNI Reactive nitrogen intermediate ROS Reactive oxygen species RTKIs Receptor tyrosine kinase inhibitors SCF Stem cell factor SDF-1 Stromal cell derived factor 1 ST-CSC Short term CSC TAF Tumor angiogenesis factor TAFs Tumor associated fibroblast TAM Tumor associated macrophages TEMs Tie2-expressing monocytes TGF-β Transforming growth factor beta TIMP-3 Tissue inhibitor of matrix metalloproteinase-3 TNF-α Tumor necrosis factor alpha TRAMP Transgenic adenocarcinoma of the mouse prostate Treg T regulatory TSP-1 Thrombospondin-1 VCAM Vascular cellular adhesion molecule VE-cadherin Vascular endothelia cadherin VEGF Vascular endothelial growth factor VEGFR1 Vascular endothelial growth factor receptor 1 VVO Vesciculo vacuolar organelles VWF Von Willebrand factor