The Tumor Microenvironment, 2010 Cancer Drug Discovery and Development Series

The fact that tumors are composed of both tumor cells and host cells has long been known. These tumor-associated cells include vascular endothelial cells and pe- cytes, as well as inflammatory cells such as neutrophils, monocytes, macrophages, mast cells and eosinophils, and lymphocytes. The tumor cells also interact with stromal cells and with elements of the tissue extracellular matrix. What has been less appreciated is the role that these cells could have in modulating the growth, invasion, and metastasis of the tumor. Early on, the elements of what we now call the tumor microenvironment were considered to be more or less innocent bysta- ers to the role of the tumor cells as they grew and invaded local sites. Today, there is an increased understanding of the critical role of the tumor microenvironment as dramatically influencing the course of tumor development and dissemination. This volume represents a superb compilation of the latest thoughts and data regarding the role of each essential component of the tumor microenvironment in cancer development and progression. Perhaps, the earliest recognition of the role of nonmalignant cells as cancer re- lators was the recognition that lymphocytes can participate in what was termed ?immune surveillance? in the 1960s. Our understanding of tumor immunity has improved markedly since then, and there are now successful clinical studies sh- ing the potential use of immune-based therapies in cancer treatment.

Preface Bruce Zetter, PhD Table of Contents: PHYSIOLOGICAL PARAMETERS 1. Combination Strategies Targeting Hypoxia Inducible Factor 1 (HIF-1) for Cancer Therapy Annamaria Rapisarda, PhD and Giovanni Melillo, MD 2. New Insights into Regulation of Tumor pH by Carbonic Anhydrases Pawel Swietach,DPhil, Adrian L. Harris, DPhil/MBChB, and Richard D. Vaughan-Jones1,PhD 3. Hypoxia, Gene Expression and Metastasis Olga V. Razorenova, PhD and Amato J. Giaccia, PhD 4. Molecular Mechanisms Regulating Expression and Function of Cancer-Associated Carbonic Anhydrase IX Jaromir Pastorek, PhD and Silvia Pastorekova, PhD 5. Glycolytic Pathway as a Target for Tumor Inhibition Weiqin Lu, PhD and Peng Huang, MD/PhD CELLULAR COMPONENTS I. MALIGNANT CELLS 6. Aberrant DNA Methylation in Cancer Cells Toshikazu Ushijima, MD/PhD 7. DNA Repair and Redox Signaling Mark R. Kelley, PhD, Millie M Georgiadis, PhD, and Melissa L. Fishel, PhD 8. Cancer Stem Cells and Microenvironment Mario Federico, MD and Antonio Giordano, MD/PhD 9. Epithelial-Mesenchymal Transition in Development and Diseases Yadi Wu,PhD and Binhua P. Zhou, MD/PhD 10. Invasion and Metastasis Douglas M. Noonan, PhD, Giuseppina Pennesi, MD, and Adriana Albini, PhD 11. Dormancy of Disseminated Tumor Cells: Reciprocal Crosstalk with the Microenvironment Paloma Bragado, PhD, Aparna C. Ranganathan, PhD, and Julio Aguirre-Ghiso, PhD II. VASCULATURE AND STROMA 12. Impact of Endothelial Progenitor Cells on Tumor Angiogenesis and Outcome of Antiangiogenic Therapy: New Perspectives on an Ongoing Controversy Robert S. Kerbel1, PhD, Francesco Bertolini, MD/PhD, and Yuval Shaked, PhD 13. Bone Marrow Derived Mesenchymal Stem/Stromal Cells and Tumor Growth Pravin J. Mishra, MS and Debabrata Banerjee, PhD 14. Integrin Signaling in Lymphangiogenesis Barbara Garmy-Susini, PhD 15. Role of Pericytes in Resistance to Anti-Angiogenic Therapy Koji Matsuo, MD, Chunhua Lu1, MD/PhD Mian M K. Shazad, MS/MD, Robert L. Coleman,MD, and Anil K. Sood, MD 16. Tumour-Promoting Stromal Fibroblasts in Human Carcinomas Urszula M. Polanska, Msc/PhD, Kieran T. Mellody, BSc./MPhil., and Akira Orimo, MD/PhD* III. IMMUNE-MEDIATED CELLS 17. Mast cells and tumor microenvironment Theoharis C. Theoharides, MS/MD/PhD, Konstantinos-Dionysios Alysandratos, MD, Asimenia Angelidou, MD, and Bodi Zhang, MD/MPH 18. Macrophages in the Tumor Microenvironment Monica Escorcio-Correia, PhD and Thorsten Hagemann, MD/PhD 19. The Prognostic Significance of Tumor-Infiltrating Lymphocytes Ping Yu, MD/PhD and Yang-Xin Fu, MD/PhD 20. The Pro-Inflammatory Milieu and Pre-Malignant Epithelial Initiation Adam Yagui-Beltran, MD, Lisa M. Coussens, PhD, Qizi Tang, PhD, and David Jablons, MD 21. Natural Killer Cells for Adoptive Immunotherapy Jonathan E. Benjamin, MD/PhD and Sally Arai, MD EXTRACELLULAR MATRIX 22. Fibronectin Andreas Menrad, PhD 23. Collagen in Cancer Janelle L. Lauer, PhD and Gregg B. Fields, PhD 24. Integrins and Cancer Laurie G. Hudson,PhD and M. Sharon Stack, PhD 25. Matrix Metalloproteinases and Cancer Cell Invasion/Metastasis Stanley Zucker, MD and Jian Cao, PhD 26. Tetraspanins and Cancer Metastasis Margot Zoller, PhD SECRETED PROTEINS 27. Chemokines and Metastasis Kalyan C. Nannuru, PhD, Seema Singh, PhD, and Rakesh K. Singh, PhD 28. Transforming Growth Factor-? in Lung Cancer, Carcinogenesis and Metastasis Sonia B. Jakowlew, PhD 29. Cooperative Interactions Between Integrins and Growth Factors in Pathological Angiogenesis Jennifer M. Roth, MS, Eric Tweedie, BS, and Peter C. Brooks, PhD 30. The Extracellular Matrix and the Growth and Survival of Tumors Yves DeClerck, MD 31. Secreted Growth Factors as Therapeutic Targets Beverly A. Teicher, PhD 32. Adrenomedullin in Tumor Development Rebecca G. Bagley, MS

Rebecca Bagley is a senior scientist at Genzyme Corporation and has worked in the biotechnology industry for 20 years with degrees in biology from Wellesley College and Harvard University. Her expertise in drug development spans a wide range of approaches including immunotherapies, gene and protein therapies, and small molecule delivery with publications in journals such as Molecular Cancer Therapeutics, Cancer Research, and Microvascular Research . Her current research focuses on stem cells, tumor vasculature, and target validation.