Hyaluronan biology is being recognized as an important regulator of cancer progression. Paradoxically, both hyaluronan (HA) and hyaluronidases, the enzymes that eliminate HA, have also been correlated with cancer progression. Hyaluronan, a long-chain polymer of the extracellular matrix, opens up tissue spaces through which cancer cells move and metastasize. It also confers motility upon cells through interactions of cell-surface HA with the cytoskeleton. Embryonic cells in the process of movement and proliferation use the same strategy. It is an example of how cancer cells have commandeered normal cellular processes for their own survival and spread. There are also parallels between cancer and wound healing, cancer occasionally being defined as a wound that does not heal.
The growing body of literature regarding this topic has recently progressed from describing the association of hyaluronan and hyaluronidase expression associated with different cancers, to understanding the mechanisms that drive tumor cell activation, proliferation, drug resistance, etc. No one source, however, discusses hyaluronan synthesis and catabolism, as well as the factors that regulate the balance. This book will offer a comprehensive summary and cutting-edge insight into Hyaluronan biology, the role of the HA receptors, the hyaluronidase enzymes that degrade HA, as well as HA synthesis enzymes and their relationship to cancer.
- Offers a comprehensive summary and cutting-edge insight into Hyaluronan biology, the role of the HA receptors, the hyaluronidase enzymes that degrade HA, as well as HA synthesis enzymes and their relationship to cancer
- Chapters are written by the leading international authorities on this subject, from laboratories that focus on the investigation of hyaluronan in cancer initiation, progression, and dissemination
- Focuses on understanding the mechanisms that drive tumor cell activation, proliferation, and drug resistance
Inhaltsverzeichnis
1;Front Cover;1 2;Hyaluronan in Cancer Biology;2 3;Copyright Page;5 4;Short Contents;8 5;Full Contents;12 6;Preface;20 7;Foreword;24 8;List of Contributors;26 9;SECTION I HISTORICAL OVERVIEW;30 9.1;CHAPTER 1 Association Between Cancer and Acid Mucopolysaccharides: An Old Concept Comes of Age, Finally;32 9.1.1;INTRODUCTION;33 9.1.2;HYALURONAN;33 9.1.3;STROMALEPITHELIAL INTERACTION IN CANCER;36 9.1.4;HYALURONAN IN CANCER;38 9.1.5;ABNORMALITIES IN OTHER GLYCOSAMINOGLYCANS OCCUR IN MALIGNANCY;40 9.1.6;CONCLUSIONS;41 10;SECTION II CELL BIOLOGY OF HYALURONAN IN CANCER;46 10.1;CHAPTER 2 Hyaluronan-CD44 Interactions and Chemoresistance in Cancer Cells;48 10.1.1;INTRODUCTION;48 10.1.2;HYALURONAN, CD44, AND DRUG RESISTANCE;49 10.1.3;CELL-AUTONOMOUS REGULATION OF CELL SURVIVAL SIGNALING PATHWAYS BY HYALURONAN AND CD44;50 10.1.4;HYALURONAN, CD44, AND DRUG TRANSPORTERS;52 10.1.5;HYALURONAN, EMMPRIN, AND THE GLYCOLYTIC PHENOTYPE;54 10.1.6;HYALURONAN, CANCER STEM CELLS, AND DRUG RESISTANCE;55 10.1.7;CONCLUSIONS;57 10.1.8;ACKNOWLEDGMENTS;58 10.2;CHAPTER 3 Growth Factor Regulation ofnbspHyaluronan Deposition innbspMalignancies;66 10.2.1;INTRODUCTION;66 10.2.2;EXPRESSION OF HYALURONAN SYNTHASES AND HYALURONIDASES;68 10.2.3;HYALURONAN SIGNALING PROMOTES THE MALIGNANT PHENOTYPE OF TUMOR CELLS;69 10.2.4;REGULATION OF HYALURONAN LEVELS PRODUCED BY TUMOR CELLS;72 10.2.5;REGULATION OF HYALURONAN SYNTHESIS BY PERITUMORAL STROMA CELLS;73 10.2.6;FUTURE PERSPECTIVES;75 10.2.7;ACKNOWLEDGMENTS;75 10.3;CHAPTER 4 Hyaluronan Binding Protein 1 (HABP1/p32/gC1qR): A New Perspective in Tumor Development;80 10.3.1;HYALURONAN BINDING PROTEIN 1 (HABP1);82 10.3.2;EVIDENCE FOR HABP1 TO BE INVOLVED IN TUMOR DEVELOPMENT;87 10.3.3;ECTOPIC EXPRESSION OF HABP1 INDUCES APOPTOSIS, AUTOPHAGIC VACUOLES, AND MITOCHONDRIAL DYSFUNCTION;90 10.3.4;ASSOCIATION OF ALLELIC LOSS AT 17P13.3 CHROMOSOME WITH CANCER INITIATION AND PROMOTION;93 10.3.5;CONCLUSION;94 10.3.6;ACKNOWLEDGEMENT;95 11;SECTION III HYALURONAN RECEPTORS AND
SIGNAL TRANSDUCTION PATHWAYS;98 11.1;CHAPTER 5 CD44 Meets Merlin and Ezrin: Their Interplay Mediates the Pro-Tumor Activity of CD44 and Tumor-Suppressing Effect of Merlin;100 11.1.1;CD44 PROMOTES TUMOR INVASION AND METASTASIS;101 11.1.2;CD44-MEDIATED SIGNALS AND THE DOWNSTREAM EFFECTORS OF CD44;103 11.1.3;MERLIN ACTS AS A TUMOR SUPPRESSOR, AND THE MUTANT FORMS OF THIS PROTEIN PROMOTE TUMORIGENESIS;105 11.1.4;THE FUNCTION OF MERLIN IS REGULATED BY ITS POSTTRANSLATIONAL MODIFICATIONS;105 11.1.5;MERLIN COUNTERACTS THE EFFECT OF EZRIN AND INHIBITS THE CD44HA INTERACTION AND CD44 FUNCTION;106 11.1.6;MERLIN IS INVOLVED IN SEVERAL IMPORTANT SIGNAL TRANSDUCTION PATHWAYS;107 11.1.7;MERLIN ACTS UPSTREAM OF THE HIPPO SIGNALING PATHWAY IN DROSOPHILA;108 11.1.8;A MODEL FOR CD44 SIGNALING THROUGH MERLIN AND THE ERM PROTEINS;110 11.1.9;ACKNOWLEDGMENTS;111 11.2;CHAPTER 6 Hyaluronan- Mediated CD44 Interaction with Receptor and Non-Receptor Kinases Promotes Oncogenic Signaling, Cytoskeleton Activation and Tumor Progression;118 11.2.1;HYALURONAN (HA) METABOLISM IN CANCER PROGRESSION;118 11.2.2;CD44 (AN HA RECEPTOR) IN TUMOR PROGRESSION;120 11.2.3;ACKNOWLEDGMENTS;130 11.3;CHAPTER 7 Adhesion and Penetration: Two Sides of CD44 Signal Transduction Cascades in the Context of Cancer Cell Metastasis;138 11.3.1;INTRODUCTION: HA, CD44, THE TUMOR MICROENVIRONMENT, AND METASTASIS;138 11.3.2;PENETRATION: CD44 PROMOTED INVASION AND INTRAVASATION;140 11.3.3;CELLCELL ADHESION: ROLE OF CD44 IN PROMOTING EXTRAVASATION;146 11.3.4;THE ROLE OF CD44 IN PROMOTING TISSUE-SPECIFIC METASTASIS;150 11.3.5;CONCLUSIONS;151 11.4;CHAPTER 8 Involvement of CD44, a Molecule with a Thousand Faces, in Cancer Dissemination;156 11.4.1;PROLOGUE;157 11.4.2;THE INTERACTION BETWEEN THE CD44 OF LB CELLS AND HYALURONATE IN VITRO STUDIES;161 11.4.3;ELUCIDATION OF HA BINDING MECHANISM IN LB CELLS;164 11.4.4;THERAPY OF THE MALIGNANT LYMPHOMA: BLOCKING THE INTERACTION BETWEEN CD44 AND ITS LIGAND BY TARGETING THE CD44 VARIANT WITH
RELEVANT ANTIBODY;167 11.4.5;GENE VACCINATION WITH CD44 VARIANT CONSTRUCT, RATHER THAN WITH STANDARD CD44 CONSTRUCT, GENERATES RESISTANCE TO TUMOR GROWTH;169 11.4.6;EPILOGUE;170 11.4.7;ACKNOWLEDGMENTS;172 11.5;CHAPTER 9 - RHAMM/HMMR: An Itinerant and Multifunctional Hyaluronan Binding Protein That Modifies CD44 Signaling and Mitotic Spindle Formation;176 11.5.1;INTRODUCTION;176 11.5.2;RHAMM AND CANCER;178 11.5.3;EXTRACELLULAR AND INTRACELLULAR RHAMM ONCOGENIC FUNCTIONS IN CULTURE;181 11.5.4;RHAMM PROTEIN FORMS CONTROL MULTIPLE SIGNALING NETWORKS;186 11.5.5;CONCLUSIONS;194 11.5.6;ACKNOWLEDGMENTS;194 12;SECTION IV HYALURONAN SYNTHESIS;198 12.1;CHAPTER 10 Altered Hyaluronan Biosynthesis in Cancer Progression;200 12.1.1;INTRODUCTION;200 12.1.2;HA BIOSYNTHESIS;201 12.1.3;ALTERED HA SYNTHESIS IN CANCER;202 12.1.4;TUMORSTROMAL INTERACTION;203 12.1.5;NOVEL FUNCTION OF HA IN STROMAL CELL RECRUITMENT;205 12.1.6;EPITHELIALMESENCHYMAL TRANSITION CAUSED BY HA OVERPRODUCTION;207 12.1.7;ROLES OF HA-RICH ECM IN TUMOR ANGIOGENESIS;208 12.1.8;CONCLUSION AND PERSPECTIVES;210 12.1.9;ACKNOWLEDGMENTS;211 13;SECTION V HYALURONAN DEGRADATION, THE HYALURONIDASES, AND THE PRODUCTS OF DEGRADATION;216 13.1;CHAPTER 11 Hyaluronidase: Both a Tumor Promoter and Suppressor;218 13.1.1;INTRODUCTION;218 13.1.2;HYALURONIDASES;219 13.1.3;HAase EXPRESSION IN TUMOR CELLS;221 13.1.4;HAase FUNCTIONS IN GENITO-URINARY TUMORS;223 13.1.5;REGULATION OF HAase GENE EXPRESSION;226 13.1.6;HAase AND SIGNALING;227 13.1.7;ACKNOWLEDGMENT;231 13.2;CHAPTER 12 Hyaluronidases in Cancer Biology;236 13.2.1;INTRODUCTION;236 13.2.2;HYALURONIDASES AND THEIR STRUCTURE;238 13.2.3;A CATABOLIC SCHEME FOR HYALURONAN;239 13.2.4;THE WARBURG EFFECT;239 13.2.5;HYALURONIDASE INHIBITORS;241 13.2.6;HYALURONIDASE INHIBITORS;241 13.2.7;HYALURONIDASE MODULATES CD44 EXPRESSION;242 13.2.8;HYALURONAN FRAGMENTATION;242 13.2.9;HYALURONIDASES AS ANTI-CANCER CHEMOTHERAPEUTIC AGENTS;244 13.2.10;HYALURONIDASES IN CANCER PROGRESSION;245 13.2.11;THE CON
UNDRUMS INVOLVING HYALURONIDASES IN MALIGNANCY;245 13.3;CHAPTER 13 Hyaluronan Fragments: Informational Polymers Commandeered by Cancers;250 13.3.1;INTRODUCTION;250 13.3.2;PRODUCTION OF HA FRAGMENTS;251 13.3.3;RECEPTORS OF HA FRAGMENTS;253 13.3.4;DIFFERENT SIZES OF HA HAVE DIFFERENT BIOLOGICAL FUNCTIONS;259 13.3.5;CONCLUSIONS AND FUTURE PROSPECTS;275 13.3.6;ACKNOWLEDGMENTS;278 14;SECTION VI HYALURONAN IN CANCER EPITHELIAL-STROMAL INTERACTIONS;284 15;CHAPTER 14 Hyaluronan in Human Tumors: Importance of Stromal and Cancer Cell-Associated Hyaluronan;286 15.1;HYALURONAN ACCUMULATION IN MALIGNANT TUMORS;287 15.2;HYALURONAN ASSOCIATED WITH CANCER CELLS;288 15.3;STROMAL ACCUMULATION OF HYALURONAN;296 15.4;MECHANISMS OF HYALURONAN ACCUMULATION IN TUMORS;299 15.5;HOW DOES HYALURONAN CONTRIBUTE TO CANCER PROGRESSION?;303 15.6;CONCLUSIONS;307 15.7;ACKNOWLEDGMENTS;307 16;CHAPTER 15 The Oncofetal Paradigm Revisited: MSF and HA as Contextual Drivers of Cancer Progression;314 16.1;INTRODUCTION;315 16.2;MSF: ITS MOLECULAR CHARACTERIZATION AND SPECTRUM OF BIOACTIVITIES;316 16.3;THE ONCOFETAL PATTERN OF MSF EXPRESSION: CONTEXTUAL CONTROL BY ECM AND SOLUBLE FACTORS;321 16.4;THE CONTEXTUAL CONTROL OF TARGET CELL RESPONSE TO MSF BY ECM AND SOLUBLE FACTORS;326 16.5;AN EXTENDED ONCOFETAL PARADIGM OF CANCER PATHOGENESIS: THE INTER DEPENDENT CONTRIBUTION OF GENETIC AND EPIGENETIC MECHANISMS;329 16.6;ACKNOWLEDGMENTS;332 17;SECTION VII HYALURONAN AND INDIVIDUAL CANCERS;336 17.1;CHAPTER 16 Hyaluronan Synthesis and Turnover in Prostate Cancer;338 17.1.1;OVERVIEW OF PROSTATE CANCER PROGRESSION;338 17.1.2;HA SYNTHASES AND HYALURONIDASES;339 17.1.3;GENETIC SUSCEPTIBILITY TO PROSTATE CANCER;340 17.1.4;INFLAMMATION RESPONSE AND HYPOXIA;340 17.1.5;TUMORIGENESIS;342 17.1.6;ANGIOGENESIS AND LYMPHANGIOGENESIS;347 17.1.7;METASTASIS AND BONE TURNOVER;348 17.2;CHAPTER 17 Role of Hyaluronan and CD44 innbspMelanoma Progression;358 17.2.1;HYALURONAN AND MELANOMA;358 17.2.2;INTERACTION OF HYALURONAN AND MELANOM
A CELLS;360 17.2.3;HYALURONAN METABOLISM, MELANOMA, AND UV-B;363 17.2.4;CONCLUSION AND PERSPECTIVES;365 17.2.5;ACKNOWLEDGMENT;366 17.3;CHAPTER 18 Role of Hyaluronan Metabolism in the Initiation, Invasion, and Metastasis of Breast Cancer;370 17.3.1;THE TUMOR MICROENVIRONMENT OF BREAST CANCER;370 17.3.2;INTRATUMORAL HYALURONAN LOCALIZATION DURING BREAST CANCER TUMORIGENESIS AND PROLIFERATION;371 17.3.3;METABOLISM OF HYALURONAN IN BREAST CANCER DYSREGULATION OF A FINELY TUNED PROCESS;372 17.3.4;THE CO-ORDINATED FUNCTION AND IMPORTANCE OF HA METABOLISM IN BREAST CANCER;382 17.3.5;CONCLUSIONS;384 18;SECTION VIII CLINICAL USES OF HYALURONAN-RELATED BIOMATERIALS AS ANTI-CANCER AGENTS;390 18.1;CHAPTER 19 Clinical Use of Hyaluronidase in Combination Cancer Chemotherapy: A Historic Perspective;392 18.1.1;INTRODUCTION;392 18.1.2;CLINICAL APPLICATION OF HYALURONIDASE IN PERIPHERAL CIRCULATORY DISORDER;394 18.1.3;CLINICAL APPLICATIONS OF HYALURONIDASE IN MALIGNANT DISEASE;394 18.1.4;HYALURONIDASE PREPARATIONS IN ADDITIONAL CLINICAL STUDIES IN VIENNA;395 18.1.5;EXTENDED STUDIES OF THE USE OF HYALURONIDASE AS ADJUNCTS IN CANCER CHEMOTHERAPY;396 18.1.6;SIDE EFFECTS OBSERVED DURING CLINICAL AND EXPERIMENTAL USES OF HYALURONIDASE;399 18.1.7;APPLICATION OF HYALURONIDASE IN EXPERIMENTAL ANIMAL MODELS OF CANCER;400 18.1.8;OVERVIEW AND ADDITIONAL OBSERVATIONS;401 18.1.9;CONCLUDING REMARKS AND SUMMARY;403 18.2;CHAPTER 20 Exploiting the Hyaluronan CD44 Interaction for Cancer Therapy;408 18.2.1;EXPLOITING THE HYALURONANCD44 INTERACTION FOR CANCER THERAPY;409 18.2.2;INTERFERENCE WITH CD44-HA INTERACTIONS;410 18.2.3;HA-INDUCED SENSITIZATION TO CHEMOTHERAPEUTICS;421 18.2.4;TARGETING CHEMOTHERAPEUTICS;421 18.2.5;CD44 MEDIATED CANCER IMMUNOTHERAPY;424 18.2.6;GENE THERAPY BY DOWN REGULATION OF CD44 PRODUCTION;425 18.2.7;GENE THERAPY BY PRODUCTION OF CYTOTOXIC GENES THROUGH CD44 REGULATION;426 18.2.8;CONCLUSION;427 18.2.9;ACKNOWLEDGMENT;428 19;SECTION IX A NEW PERSPECTIVE;434 20;CHAPTER 21 Hyaluro
nidase-2 and Its Role as a Cell-Entry Receptor for Sheep Retroviruses That Cause Contagious Respiratory Tract Cancers;436 20.1;ONCOGENIC SHEEP RETROVIRUSES;436 20.2;IDENTIFICATION OF HYAL-2 AS THE CELL-ENTRY RECEPTOR FOR JSRV AND ENTV;438 20.3;HYAL-2 LOCATION AND ENZYMATIC ACTIVITY;441 20.4;HYAL-2 ROLE IN SHEEP RETROVIRUS ONCOGENESIS?;443 20.5;HYAL-2 ROLE IN SHEEP PLACENTAL MORPHOGENESIS;445 20.6;ACKNOWLEDGMENTS;445 21;Index;448 22;Color Plate;456
