1. Explains role of the tumor microenvironment as dramatically influencing the course of tumor development and dissemination2. Represents a superb compilation of the latest thoughts and data regarding the role of each essential component of the tumor microenvironment3. In-depth chapters written by known professionals in the field
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.
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.
PrefaceBruce Zetter, PhDTable of Contents:PHYSIOLOGICAL PARAMETERS1. Combination Strategies Targeting Hypoxia Inducible Factor 1 (HIF-1) for Cancer TherapyAnnamaria Rapisarda, PhD and Giovanni Melillo, MD 2. New Insights into Regulation of Tumor pH by Carbonic AnhydrasesPawel Swietach,DPhil, Adrian L. Harris, DPhil/MBChB, and Richard D. Vaughan-Jones1,PhD3. Hypoxia, Gene Expression and MetastasisOlga V. Razorenova, PhD and Amato J. Giaccia, PhD4. Molecular Mechanisms Regulating Expression and Function of Cancer-Associated Carbonic Anhydrase IXJaromir Pastorek, PhD and Silvia Pastorekova, PhD 5. Glycolytic Pathway as a Target for Tumor InhibitionWeiqin Lu, PhD and Peng Huang, MD/PhDCELLULAR COMPONENTSI. MALIGNANT CELLS6. Aberrant DNA Methylation in Cancer CellsToshikazu Ushijima, MD/PhD 7. DNA Repair and Redox SignalingMark R. Kelley, PhD, Millie M Georgiadis, PhD, and Melissa L. Fishel, PhD 8. Cancer Stem Cells and MicroenvironmentMario Federico, MD and Antonio Giordano, MD/PhD9. Epithelial-Mesenchymal Transition in Development and DiseasesYadi Wu,PhD and Binhua P. Zhou, MD/PhD10. Invasion and MetastasisDouglas M. Noonan, PhD, Giuseppina Pennesi, MD, and Adriana Albini, PhD11. Dormancy of Disseminated Tumor Cells: Reciprocal Crosstalk with the MicroenvironmentPaloma Bragado, PhD, Aparna C. Ranganathan, PhD, and Julio Aguirre-Ghiso, PhDII. VASCULATURE AND STROMA12. Impact of Endothelial Progenitor Cells on Tumor Angiogenesis and Outcome of Antiangiogenic Therapy: New Perspectives on an Ongoing ControversyRobert 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 TherapyKoji Matsuo, MD, Chunhua Lu1, MD/PhD Mian M K. Shazad, MS/MD, Robert L. Coleman,MD, and Anil K. Sood, MD16. Tumour-Promoting Stromal Fibroblasts in Human CarcinomasUrszula M. Polanska, Msc/PhD, Kieran T. Mellody, BSc./MPhil., and Akira Orimo, MD/PhD*III. IMMUNE-MEDIATED CELLS17. Mast cells and tumor microenvironmentTheoharis C. Theoharides, MS/MD/PhD, Konstantinos-Dionysios Alysandratos, MD, Asimenia Angelidou, MD, and Bodi Zhang, MD/MPH 18. Macrophages in the Tumor MicroenvironmentMonica Escorcio-Correia, PhD and Thorsten Hagemann, MD/PhD 19. The Prognostic Significance of Tumor-Infiltrating LymphocytesPing Yu, MD/PhD and Yang-Xin Fu, MD/PhD20. The Pro-Inflammatory Milieu and Pre-Malignant Epithelial InitiationAdam Yagui-Beltran, MD, Lisa M. Coussens, PhD, Qizi Tang, PhD, and David Jablons, MD21. Natural Killer Cells for Adoptive ImmunotherapyJonathan E. Benjamin, MD/PhD and Sally Arai, MDEXTRACELLULAR MATRIX22. FibronectinAndreas Menrad, PhD23. Collagen in CancerJanelle L. Lauer, PhD and Gregg B. Fields, PhD24. Integrins and CancerLaurie G. Hudson,PhD and M. Sharon Stack, PhD25. Matrix Metalloproteinases and Cancer Cell Invasion/MetastasisStanley Zucker, MD and Jian Cao, PhD26. Tetraspanins and Cancer MetastasisMargot Zoller, PhDSECRETED PROTEINS27. Chemokines and MetastasisKalyan C. Nannuru, PhD, Seema Singh, PhD, and Rakesh K. Singh, PhD28. Transforming Growth Factor-? in Lung Cancer, Carcinogenesis and MetastasisSonia 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, PhD30. The Extracellular Matrix and the Growth and Survival of TumorsYves DeClerck, MD 31. Secreted Growth Factors as Therapeutic TargetsBeverly A. Teicher, PhD 32. Adrenomedullin in Tumor Development Rebecca G. Bagley, MS
The field of cancer biology and developmental therapeutics is continually evolving as new methodologies are developed and new targets are discovered. Although multiple therapeutics directly target the malignant cells these drugs rarely prevent recurrence of disease or the progression of metastasis. The complex biology of tumors presents challenges in designing treatments that will eliminate the malignant cells as well as the supporting network of vasculature and stroma that allows for the comparison of tumors to developing organs in embryos. In addition to blood vessels and malignant cells, tumors consist of fibroblasts, immune and inflammatory cells, and a myriad of proteins that comprise the extracellular matrix. Effective eradication of malignant disease requires therapeutic strategies that factor in targeting the tumor microenvironment. In the past decade, a new class of anticancer drugs has emerged that interferes with tumor angiogenesis; however the clinical benefit from treatment with the first generation antiangiogenic agents added to the standard of care is often modest. Thus, there remains a critical need to understand the tumor microenvironment and to develop anti-cancer therapies that address this aspect of malignant disease.The first edition of The Tumor Microenvironment is intended to give a current perspective on the role of the tumor microenvironment in malignant progression and detail strategies for novel therapies directed towards the cellular matrix. This book explores the many biological and physiological aspects of the tumor as a tissue and includes chapters on the variety of cells that influence tumor growth and spread as well as the cell-associated and soluble proteins that can promote invasion and metastasis. Several chapters describe endothelial cells and pericytes that form tumor vasculature. Insights into the role of progenitor and stem cells are included. The contribution of the supporting stroma is addressed in addition to cell-cell signaling and cell-matrix interactions. Additional chapters describe the influence of infiltrating cells of the immune system on tumor growth. The Tumor Microenvironment is the definitive text detailing cutting edge research by experts in the field and will be a valued resource in the study of this important area of cancer biology for many years to come.
This book explores the many biological and physical aspects of the tumor microenvironment. It represents a superb compilation of the latest thoughts and data on this topic, and the in-depth chapters are written by known professionals in the field. This book will explore the many biological and physical aspects of the tumor microenvironment. The book will include chapters on the various cells that influence tumor growth and function as well as the cell-associated and soluble proteins that can promote invasion and metastasis. Several chapters will describe endothelial cells and pericytes that form tumor vasculature. Insights on the role of progenitor and stem cells will be included. The contribution of the supporting stroma will be addressed in addition to cell-cell signaling and cell-matrix interactions. Additional chapters will describe the influence of infiltrating cells of the immune system on tumor growth.
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.
Physiological Parameters.- Combination Strategies Targeting Hypoxia Inducible Factor 1 (HIF-1) for Cancer Therapy.- The Tumor Microenvironment: New Insights into Regulation of Tumor pH by Carbonic Anhydrases.- Hypoxia, Gene Expression, and Metastasis.- Molecular Mechanisms Regulating Expression and Function of Cancer-Associated Carbonic Anhydrase IX.- Glycolytic Pathway as a Target for Tumor Inhibition.- Malignant Cells.- Aberrant DNA Methylation in Cancer Cells.- DNA Repair and Redox Signaling.- Cancer Stem Cells and Microenvironment.- Epithelial-Mesenchymal Transition in Development and Diseases.- Invasion and Metastasis.- Dormancy of Disseminated Tumor Cells: Reciprocal Crosstalk with the Microenvironment.- Vasculature And Stroma.- Impact of Endothelial Progenitor Cells on Tumor Angiogenesis and Outcome of Antiangiogenic Therapy: New Perspectives on an Ongoing Controversy.- Bone Marrow Derived Mesenchymal Stem/Stromal Cells and Tumor Growth.- Integrin Signaling in Lymphangiogenesis.- Role of Pericytes in Resistance to Antiangiogenic Therapy.- Tumour-Promoting Stromal Myofibroblasts in Human Carcinomas.- Immune-Mediated Cells.- Mast Cells and Tumor Microenvironment.- Macrophages in the Tumor Microenvironment.- The Prognostic Significance of Tumor-Infiltrating Lymphocytes.- The Pro-inflammatory Milieu and Its Role in Malignant Epithelial Initiation.- Natural Killer Cells for Adoptive Immunotherapy.- Extracellular Matrix.- Fibronectin.- Collagen in Cancer.- Integrins and Cancer.- Matrix Metalloproteinases and Cancer Cell Invasion/Metastasis.- Tetraspanins and Cancer Metastasis.- Secreted Proteins.- Chemokines and Metastasis.- Transforming Growth Factor-? in Lung Cancer, Carcinogenesis, and Metastasis.- Cooperative Interactions Between Integrins and Growth FactorSignaling in Pathological Angiogenesis.- The Extracellular Matrix and the Growth and Survival of Tumors.- Secreted Growth Factors as Therapeutic Targets.- Adrenomedullin.
Über den Autor
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.
Inhaltsverzeichnis
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
Klappentext
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.
Explains role of the tumor microenvironment as dramatically influencing the course of tumor development and dissemination
n
Represents a superb compilation of the latest thoughts and data regarding the role of each essential component of the tumor microenvironment
n
In-depth chapters written by known professionals in the field
n
