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- BookIsrael Vlodavsky, Ralph D. Sanderson, Neta Ilan, editors.Summary: Proteases and their involvement in cancer progression have been well addressed and documented; however, the emerging premise presented within this book is that Heparanase is a master regulator of aggressive cancer phenotypes and crosstalk with the tumor microenvironment. This endoglycosidase contributes to tumor-mediated remodeling of the extracellular matrix and cell surfaces, augmenting the bioavailability of pro-tumorigenic and pro-inflammatory growth factors and cytokines that are bound to Heparan sulfate. Compelling evidence ties Heparanase with all steps of tumor progression including tumor initiation, growth, angiogenesis, metastasis, and chemoresistance, supporting the notion that Heparanase is an important contributor to the poor outcome of cancer patients and a validated target for therapy. Unlike Heparanase, heparanase-2, a close homolog of Heparanase, lacks enzymatic activity, inhibits Heparanase, and regulates selected genes that promote normal differentiation and tumor suppression. Written by internationally recognized leaders in Heparanase biology, this volume presents a comprehensive understanding of Heparanase's multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications to scientists, clinicians and advanced students in cell biology, tumor biology and oncology.
Contents:
Intro
Contents
Contributors
About the Editors
Part I: Historical and General Background
Chapter 1: Forty Years of Basic and Translational Heparanase Research
1.1 Historical Introduction
1.1.1 Key Observations Made Prior to Cloning of the HPSE Gene (Chronological Order)
1.2 Heparanase Gene Cloning
1.3 Studies Performed Following Cloning of the HPSE Gene
1.3.1 Introductory Notes
1.3.2 Key Observations Made After Cloning of the HPSE Gene
Structural Aspects
Gene Regulation
Angiogenesis & Metastasis
Animal Models Heparanase Uptake and Cellular Traffic
Nuclear Heparanase and Its Transcriptional Activity
Heparanase Non-Enzymatic and Signaling Function
Heparanase Inhibitors
Various Tumors
Multiple Myeloma
Tumor Microenvironment
Inflammation and Cells of the Immune System
Vaccination
Diabetes, Diabetic Complications and Other Disorders
Aterosclerosis & Thrombosis
Viral Infection
1.4 Concluding Remarks and Perspectives
References
Chapter 2: Heparanase - Discovery and Targets
2.1 Introduction
2.2 Heparanase, Early Findings 2.3 Stereochemistry of Heparanase Target
2.4 How Many Heparanases?
2.5 Heparanase and Polysaccharide Metabolism
2.6 Heparanase and the GAGosome
References
Chapter 3: Heparanase: Historical Aspects and Future Perspectives
3.1 Introduction
3.2 Historical Overview and General Properties of Heparanase
3.3 Overview of Substrate Specificity of Heparanase
3.4 Functions Dependent on Heparanase Enzymatic Activity
3.4.1 HS Turnover
3.4.2 Involvement in Cell Invasion
3.4.3 Involvement in Release of ECM Bound Proteins 3.4.4 Involvement in Depletion of Intracellular Anti-Oxidant Stores of HS
3.4.5 Facilitator of Spread of HS-Binding Viruses
3.4.6 Inhibitors of Heparanase Enzymatic Activity
3.5 Functions Independent of Heparanase Enzymatic Activity
3.5.1 Cell Adhesion Molecule
3.5.2 Promoter of Signal Transduction
3.5.3 Transcription Factor
3.6 Future Perspectives
3.6.1 How Does Heparanase Initiate Signalling Pathways?
3.6.2 Do Nuclear Heparanase and HS Interact?
3.6.3 Relationship Between Heparanase-1 and Heparanase-2
3.6.4 Drug Development: Where to Next? 3.7 Concluding Remarks
References
Chapter 4: Involvement of Syndecan-1 and Heparanase in Cancer and Inflammation
4.1 Introduction
4.1.1 The Syndecan Family of Heparan Sulfate Proteoglycans
4.1.2 Heparanase - A Key Enzyme in ECM Remodeling
4.2 The Heparanase-Syndecan Axis
4.2.1 Heparanase Mediated Sdc1 Shedding
4.2.2 Heparanase and Sdc1 in the Nucleus
4.2.3 Effects on Exosome Formation and Function
4.2.4 Effects on Growth Factor Signaling
4.3 Functional Cooperation of Syndecan-1 and Heparanase in Inflammation
4.3.1 Lessons from Mouse Models Role of Sdc1 and Heparanase in Delayed-Type Hypersensitivity