TUMOR MICROENVIRONMENT AND MYELOMONOCYTIC CELLS Edited by Subhra K. Biswas Tumor Microenvironment and Myelomonocytic Cells Edited by Subhra K. Biswas Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Maja Jukic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published March, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Tumor Microenvironment and Myelomonocytic Cells, Edited by Subhra K. Biswas p. cm. ISBN 978-953-51-0439-1 Contents Preface IX Part 1 Myelomonocytic Cells – Phenotypic and Functional Diversity in Tumor Microenvironment 1 Chapter 1 Cell Lineage Commitment and Tumor Microenvironment as Determinants for Tumor-Associated Myelomonocytic Cells Plasticity 3 Raffaella Bonecchi, Benedetta Savino, Matthieu Pesant and Massimo Locati Chapter 2 Functions of Diverse Myeloid Cells in the Tumor Micro-Environment 17 A. Sica, C. Porta, E. Riboldi, M. Erreni and P. Allavena Chapter 3 Monocyte Subsets and Their Role in Tumor Progression 43 Andrea I. Doseff and Arti Parihar Chapter 4 Myeloid Derived Suppressor Cells: Subsets, Expansion, and Role in Cancer Progression 63 Liang Zhi, Benjamin Toh and Jean-Pierre Abastado Chapter 5 The Role of Hypoxia in Re-Educating Macrophages in the Tumour Environment 89 Reuben J. Harwood, Claire E. Lewis and Subhra K. Biswas Chapter 6 Tumor Inflammatory Microenvironment in EMT and Metastasis 111 Tingting Yuan, Yadi Wu and Binhua P. Zhou Part 2 Tumor Microenvironment and Myelomonocytic Cell Interaction in Specific Cancer Subtypes 135 Chapter 7 Lung Tumor Microenvironment and Myelomonocytic Cells 137 Minu K. Srivastava, Åsa Andersson, Li Zhu, Marni Harris-White, Jay M. Lee, Steven Dubinett and Sherven Sharma VI Contents Chapter 8 Immunobiology of Monocytes/Macrophages in Hepatocellular Carcinoma 157 Dong-Ming Kuang and Limin Zheng Chapter 9 Macrophages and Microglia in Brain Malignancies 173 Cristina Riccadonna and Paul R. Walker Chapter 10 The Role of Tumor Microenvironment in Oral Cancer 201 Masakatsu Fukuda, Yoshihiro Ohmori and Hideaki Sakashita Part 3 Regulation of Tumor Microenvironment – New Players and Approaches 219 Chapter 11 Modulation of Cancer Progression by Tumor Microenvironmental Leukocyte-Expressed microRNAs 221 Lorenzo F. Sempere and Jose R. Conejo-Garcia Chapter 12 The Role of Mesenchymal Stem Cells in the Tumor Microenvironment 255 Aline M. Betancourt and Ruth S. Waterman Chapter 13 Visualisation of Myelomonocytic Cells in Tumors 287 Tatyana Chtanova and Lai Guan Ng Preface Tumor microenvironment represents an extremely dynamic and diverse milieu consisting of different cell types (e.g. tumor cells, stromal cells), distinct physico- chemical stimuli (e.g. low oxygen or hypoxia) and a variety of humoral factors such as cytokines, chemokines and growth factors. The interplay of these different elements is crucial to tumor progression. Therefore, investigating the tumor microenvironment has a direct impact on the understanding of the mechanisms which regulate cancer progression. Myelomonocytic cells have emerged as key players in the tumor microenvironment. In particular, tumor associated macrophages (TAMs) have served as the classical example of the tumor promoting actions of myelomonocytic cells. These cells constitute a major proportion of the inflammatory infiltrates associated with most solid tumors and a link between inflammation and cancer. One of the most direct evidence for the tumor promoting role of TAMs comes from studies which use transgenic approach to modulate TAM numbers in murine tumor models where TAM infiltration has been linked to tumor progression, angiogenesis and metastasis. Similarly, in many human cancers of the breast, cervix, bladder and prostrate, a high TAM density positively correlates with poor prognosis. More recently, other myelomonocytic cell types such as blood monocytes, Tie-2-Expressing Monocytes (TEMs), Myeloid-Derived Suppressor Cells (MDSCs), and Tumor Associated Neutrophils (TANs) have been shown to possess protumoral activity. Inspite of these evidences, several aspects of myelomonocytic cell repertoire in the tumor microenvironment remains to be understood. For example, the plasticity of these cells across different phases of cancer progression, the dialogue between these cells and other lymphocytic populations in the tumor tissues, and the possibility of re- programming the tumor microenvironment by strategies to modulate myelomonocytic cells in vivo. The objective of this book is to present a comprehensive overview of the dynamic interaction between the tumor microenvironment and the myelomonocytic cells that leads to cancer progression. The focus is explaining how the tumor microenvironment polarizes the myelomonocytic cells to favor tumor growth and how these cells, in turn, contribute to the shaping and maintenance of the tumor microenvironment. Mechanisms regulating this process at the level of functional phenotypes, X Preface cytokine/chemokine circuits and molecular pathways have also been addressed. For the reader's ease, the book is divided into three broad sections: section 1 introduces some of the basic features of myelomonocytic cells and details the general functions and the diversity of these cells in the tumor microenvironment; Section 2 focusses on describing the tumor microenvironments of specific cancer types, such as brain cancer, liver cancer, oral cancer, lung cancer and melanoma and the role of myelomonocytic cells therein; Section 3 focusses on describing some new players (e.g. mesenchymal stem cells, microRNAs) and novel approaches (e.g. in vivo imaging) of studying the tumor microenvironments. In the end, I would like to express my sincere gratitude to Profs Alberto Mantovani, Antonio Sica and Ajit Sodhi for mentoring me in the field of macrophage research. I am indebted to Saki, for her constant support and encouragement; to Prof. B. Lahiry for kindling my curiosity to look into the unknown. I am grateful to all my collaborators who have contributed to my research and the generous grant support from Biomedical Research Council (A*STAR). Finally, I would like to thank Maja and her colleagues at In Tech without whose help the production of this book would not have taken place. Subhra K. Biswas, PhD Principal Investigator Singapore Immunology Network (SIgN), Agency for Science, Technology & Research (A*STAR), 8A Biomedical Grove; #04 Immunos, Singapore . TUMOR MICROENVIRONMENT AND MYELOMONOCYTIC CELLS Edited by Subhra K. Biswas Tumor Microenvironment and Myelomonocytic Cells Edited by Subhra K. Biswas . this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Tumor Microenvironment and Myelomonocytic Cells, Edited by Subhra K. Biswas. Masakatsu Fukuda, Yoshihiro Ohmori and Hideaki Sakashita Part 3 Regulation of Tumor Microenvironment – New Players and Approaches 219 Chapter 11 Modulation of Cancer Progression by Tumor Microenvironmental