Karamanos Extracellular Matrix: Pathobiology and Signaling
1. Auflage 2012
ISBN: 978-3-11-025877-6
Verlag: De Gruyter
Format: PDF
Kopierschutz: 1 - PDF Watermark
E-Book, Englisch, 938 Seiten
ISBN: 978-3-11-025877-6
Verlag: De Gruyter
Format: PDF
Kopierschutz: 1 - PDF Watermark
Over the last decades cell biology and biological chemistry have increasingly turned their attention to the space between cells and revealed an elaborate network of macromolecules essential for structural support, cell migration, adhesion and signaling. This comprehensive handbook of the extracellular matrix is organized into seven thematic sections, giving an overview of the current state of knowledge of matrix components (structure and function), their roles in health and disease (matrix pathobiology) as well as new concepts of pharmacological targeting.
Zielgruppe
Researchers in biochemistry, molecular and cellular biology, medicine, biotechnology, pharmaceutical industries
Autoren/Hrsg.
Fachgebiete
- Naturwissenschaften Biowissenschaften Biochemie (nichtmedizinisch)
- Technische Wissenschaften Verfahrenstechnik | Chemieingenieurwesen | Biotechnologie Biotechnologie Medizinische Biotechnologie
- Naturwissenschaften Biowissenschaften Zellbiologie
- Naturwissenschaften Biowissenschaften Molekularbiologie
- Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizinische Fachgebiete Pharmakologie, Toxikologie
- Technische Wissenschaften Verfahrenstechnik | Chemieingenieurwesen | Biotechnologie Pharmazeutische Technologie
- Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Pharmazie
- Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Vorklinische Medizin: Grundlagenfächer Molekulare Medizin, Zellbiologie
Weitere Infos & Material
1;Preface;19
2;Comments on the book Extracellular Matrix: Pathobiology & Signaling by Dick Heinegård;23
3;About the Editor/Section Editors;25
4;List of contributing authors;29
5;Abbreviations and acronyms used;39
6;1 An introduction to the extracellular matrix molecules and their importance in pathobiology and signaling;51
6.1;1.1 Extracellular matrix: a functional scaffold;53
6.1.1;1.1.1 ECM components: structural and functional properties;54
6.1.2;1.1.2 Matrix remodeling is accomplished by proteolytic enzymes;62
6.1.3;1.1.3 Cell surface receptors mediate cell-cell and cell-matrix interactions;64
6.1.4;1.1.4 Take-home message;67
7;2 Insights into the function of glycans;71
7.1;2.1 Introduction;73
7.2;2.2 Metabolic control of hyaluronan synthesis;76
7.2.1;2.2.1 Introduction;76
7.2.2;2.2.2 Transcription of hyaluronan synthases;77
7.2.3;2.2.3 UDP-sugar substrates as limiting factors in hyaluronan synthesis;79
7.2.4;2.2.4 Posttranslational processing of HAS;82
7.2.5;2.2.5 Challenges and future prospects;85
7.2.6;2.2.6 Take-home message;85
7.3;2.3 Multiple roles of hyaluronan as a target and modifier of the inflammatory response;89
7.3.1;2.3.1 Introduction;89
7.3.2;2.3.2 Endothelial permeability;90
7.3.3;2.3.3 Angiogenesis;90
7.3.4;2.3.4 Mechanisms of hyaluronan degradation;91
7.3.5;2.3.5 Consequences of hyaluronan fragmentation;91
7.3.6;2.3.6 Hyaluronan cross-talk with leukocytes;92
7.3.7;2.3.7 Adhesion of leukocytes to hyaluronan;96
7.3.8;2.3.8 Hyaluronan removal in the late phase of inflammation;98
7.3.9;2.3.9 Local clearance of hyaluronan;98
7.3.10;2.3.10 Chronic inflammation;99
7.3.11;2.3.11 Hyaluronan increase in wounds;100
7.3.12;2.3.12 Support of migration and proliferation;101
7.3.13;2.3.13 TGF-ß and myofibroblasts;102
7.3.14;2.3.14 Therapeutic applications;103
7.3.15;2.3.15 Future perspectives;103
7.3.16;2.3.16 Take-home message;104
7.4;2.4 Roles of sulfated and nonsulfated glycosaminoglycans in cancer growth and progression-therapeutic implications;116
7.4.1;2.4.1 Introduction;116
7.4.2;2.4.2 Heparin and heparan sulfate affect key tumor cell functions;117
7.4.3;2.4.3 Chondroitin sulfate participates in cancer cell, tumor stroma, and tumor microenvironement interactions to affect cancer progression;120
7.4.4;2.4.4 HA synthesis is correlated to cancer progression;122
7.4.5;2.4.5 Challenges and future prospects;124
7.4.6;2.4.6 Take-home message;126
7.5;2.5 Heparan sulfate design: regulation of biosynthesis;134
7.5.1;2.5.1 Heparan sulfate – an extracellular component with variable structure;134
7.5.2;2.5.2 How is heparan sulfate synthesized and which enzymes contribute?;135
7.5.3;2.5.3 Fine-tuning of heparan sulfate structure in the right place, at the right time;138
7.5.4;2.5.4 Disturbed heparan sulfate biosynthesis in human pathobiology;142
7.5.5;2.5.5 Take-home message;143
7.6;2.6 Bone and skin disorders caused by a disturbance in the biosynthesis of chondroitin sulfate and dermatan sulfate;148
7.6.1;2.6.1 Introduction;148
7.6.2;2.6.2 Biosynthetic pathways of CS and DS chains;150
7.6.3;2.6.3 Human congenital disorders caused by mutations of the enzymes involved in the biosynthesis of CS and DS;155
7.6.4;2.6.4 Challenges and future prospects;158
7.6.5;2.6.5 Take-home message;162
7.6.6;2.6.6 Abbreviations;162
7.7;2.7 Biological functions of branched N-glycans related to physiology and pathology of extracellular matrix;169
7.7.1;2.7.1 Introduction;169
7.7.2;2.7.2 Synthesis of branched N-glycans;169
7.7.3;2.7.3 Effect of N-glycosylation on ECM formation;172
7.7.4;2.7.4 Complexity of N-glycan branch modulates cellular functions via clustering cell surface proteins;173
7.7.5;2.7.5 Branched N-glycans regulate the biological functions of integrins;174
7.7.6;2.7.6 The mutual regulation of N-glycosylation and cadherins;175
7.7.7;2.7.7 Challenges and future prospects;176
7.7.8;2.7.8 Take-home message;177
8;3 Proteoglycans: structure, pathobiology, and signaling;183
8.1;3.1 Introduction;185
8.2;3.2 Aggrecan in skeletal development and regenerative medicine;191
8.2.1;3.2.1 Introduction;191
8.2.2;3.2.2 Aggrecan in skeletal development;191
8.2.3;3.2.3 Aggrecan in regenerative medicine;194
8.2.4;3.2.4 Take-home message;198
8.3;3.3 The pathobiology of versican;204
8.3.1;3.3.1 Introduction;204
8.3.2;3.3.2 Cardiovascular disease;204
8.3.3;3.3.3 Cancer;209
8.3.4;3.3.4 Lung;211
8.3.5;3.3.5 Eye;211
8.3.6;3.3.6 Concluding remarks;212
8.3.7;3.3.7 Take-home message;213
8.4;3.4 The biology of perlecan and its bioactive modules;221
8.4.1;3.4.1 Introduction;221
8.4.2;3.4.2 Discovery;221
8.4.3;3.4.3 Expression and localization;221
8.4.4;3.4.4 Protein family;222
8.4.5;3.4.5 The HSPG2 gene;222
8.4.6;3.4.6 Domain structure and known interactions;223
8.4.7;3.4.7 Genetic links to diseases;226
8.4.8;3.4.8 Genetic models;226
8.4.9;3.4.9 Perlecan role in cancer;227
8.4.10;3.4.10 Perlecan role in vascular biology and angiogenesis;228
8.4.11;3.4.11 Conclusions and future directions;230
8.4.12;3.4.12 Take-home message;231
8.5;3.5 Small leucine-rich proteoglycans: multifunctional signaling effectors;235
8.5.1;3.5.1 Introduction;235
8.5.2;3.5.2 Physiological functions;235
8.5.3;3.5.3 Pathobiology of class I SLRPs;236
8.5.4;3.5.4 Pathobiology of class II SLRPs;239
8.5.5;3.5.5 Pathobiology of class III SLRPs;240
8.5.6;3.5.6 Take-home message;241
8.6;3.6 Structure and function of syndecans;247
8.6.1;3.6.1 Syndecan stucture;247
8.6.2;3.6.2 Function of syndecans;249
8.6.3;3.6.3 Syndecan domains and their roles;251
8.6.4;3.6.4 Take-home message;254
8.7;3.7 The glypican family;259
8.7.1;3.7.1 The structure of glypicans;259
8.7.2;3.7.2 The functions of glypicans;260
8.7.3;3.7.3 Pathobiology of glypicans;264
8.7.4;3.7.4 Future research;266
8.7.5;3.7.5 Take-home message;266
8.8;3.8 Serglycin proteoglycan: implications for thrombosis, inflammation, atherosclerosis, and metastasis;271
8.8.1;3.8.1 Introduction;271
8.8.2;3.8.2 Cloning and cell and tissue localization of serglycin;271
8.8.3;3.8.3 Cell-specific serglycin structure;272
8.8.4;3.8.4 Regulation of serglycin expression;272
8.8.5;3.8.5 Binding of cell-specific serglycin to biologically active proteins;272
8.8.6;3.8.6 Serglycin in hematopoietic cells;273
8.8.7;3.8.7 Serglycin in nonhematopoietic cells;274
8.8.8;3.8.8 The serglycin knockout mouse;275
8.8.9;3.8.9 Challenges and future prospects;277
8.8.10;3.8.10 Take-home message;278
9;4 Matrix proteinases: biological significance in health and disease;283
9.1;4.1 Introduction;285
9.2;4.2 Extracellular functions of cysteine proteases;289
9.2.1;4.2.1 Introduction;289
9.2.2;4.2.2 Cysteine proteases and their inhibitors;290
9.2.3;4.2.3 Endogenous inhibitors of cysteine proteases;291
9.2.4;4.2.4 Cysteine proteases and their inhibitors in diseases;294
9.2.5;4.2.5 Pharmacological targeting of cysteine proteases;301
9.2.6;4.2.6 Take-home message;303
9.3;4.3 Plasmin and the plasminogen activator system in health and disease;311
9.3.1;4.3.1 Introduction;311
9.3.2;4.3.2 Plasmin;311
9.3.3;4.3.3 Plasminogen activators;316
9.3.4;4.3.4 Inhibitors of plasminogen activators;320
9.3.5;4.3.5 Plasmin substrates;321
9.3.6;4.3.6 Inhibitors of plasmin;324
9.3.7;4.3.7 Plasmin system in cancer;325
9.3.8;4.3.8 Take-home message;327
9.4;4.4 Matrix metalloproteinase complexes and their biological significance;341
9.4.1;4.4.1 Introduction;341
9.4.2;4.4.2 MMP structure and classification;343
9.4.3;4.4.3 MMP complexes;344
9.4.4;4.4.4 Take-home message;358
9.5;4.5 The ADAMTS family of metalloproteinases;365
9.5.1;4.5.1 Introduction;365
9.5.2;4.5.2 The ADAMTS family;367
9.5.3;4.5.3 Three-dimensional structures of ADAMTSs;370
9.5.4;4.5.4 Procollagen N-proteinases (ADAMTS2, 3, and 14);372
9.5.5;4.5.5 Aggrecanases;373
9.5.6;4.5.6 Inhibition of angiogenesis by ADAMTSs;377
9.5.7;4.5.7 Von Willebrand factor-cleaving proteinase: ADAMTS13;378
9.5.8;4.5.8 ADAMTS18 and dissolution of platelet aggregates;379
9.5.9;4.5.9 Atherosclerosis;380
9.5.10;4.5.10 ADAMTSs and morphogenesis;380
9.5.11;4.5.11 Wound healing;382
9.5.12;4.5.12 Ovulation;383
9.5.13;4.5.13 Future prospects;384
9.5.14;4.5.14 Take-home message;384
9.6;4.6 Proteinases in wound healing;393
9.6.1;4.6.1 Introduction;393
9.6.2;4.6.2 Overview of cutaneous wound repair;393
9.6.3;4.6.3 Hemostasis and inflammation;394
9.6.4;4.6.4 Reepithelialization;395
9.6.5;4.6.5 Granulation tissue formation;395
9.6.6;4.6.6 Tissue remodeling and wound maturation;396
9.6.7;4.6.7 Growth factors and cytokines regulating cutaneous wound healing;396
9.6.8;4.6.8 Proteolysis in cutaneous wound healing;398
9.6.9;4.6.9 PA-plasmin system;398
9.6.10;4.6.10 Matrix metalloproteinases;401
9.6.11;4.6.11 ADAM proteinases;406
9.6.12;4.6.12 ADAMTS proteinases;407
9.6.13;4.6.13 TIMPs and chemical targeting of metalloproteinases;408
9.6.14;4.6.14 Proteolysis in aberrant cutaneous wound healing;409
9.6.15;4.6.15 Targeting proteolysis – applications for wound-healing therapy;413
9.6.16;4.6.16 Take-home message;414
9.7;4.7 Rock, paper, and molecular scissors: regulating the game of extracellular matrix homeostasis, remodeling, and inflammation;427
9.7.1;4.7.1 Proteases;427
9.7.2;4.7.2 Matrix metalloproteinases;428
9.7.3;4.7.3 Natural inhibitors of MMPs;430
9.7.4;4.7.4 MMPs in cancer;431
9.7.5;4.7.5 MMPs in Inflammation;433
9.7.6;4.7.6 MMP inhibitors and clinical trials;434
9.7.7;4.7.7 The protease web;435
9.7.8;4.7.8 Degradomics;435
9.7.9;4.7.9 The CLIP-CHIP, a dedicated and focused microarray for every protease and inhibitor;436
9.7.10;4.7.10 Classic biochemical approaches;436
9.7.11;4.7.11 Sodium dodecyl sulfate polyacrylamide gel electrophoresis, zymography, mass spectrometry, and high-performance liquid chromatography;437
9.7.12;4.7.12 Proteomic identification of protease cleavage site specificity;438
9.7.13;4.7.13 Yeast two-hybrid analyses: exosite scanning and inactive-catalytic-domain capture;438
9.7.14;4.7.14 Amino-terminal-oriented mass spectrometry of substrates;439
9.7.15;4.7.15 Quantitative N- and C-terminal proteomics for substrate discovery;439
9.7.16;4.7.16 N-terminal combined fractional diagonal chromatography;440
9.7.17;4.7.17 N-terminal amine isotopic labeling of substrates;441
9.7.18;4.7.18 C terminomics and C-terminal amine-based isotope labeling of substrates;442
9.7.19;4.7.19 Perspectives and Take-home message;443
10;5 ECM cell surface receptors;451
10.1;5.1 Introduction;453
10.2;5.2 Integrin function in heart fibrosis: mechanical strain, transforming growth factor-beta 1 activation, and collagen glycation;456
10.2.1;5.2.1 Introduction;456
10.2.2;5.2.2 Cardiac fibrosis – the players;457
10.2.3;5.2.3 ECM posttranslational modifications in fibrosis: type 1 and type 2 diabetes;461
10.2.4;5.2.4 Interaction of integrins with glycated collagen;465
10.2.5;5.2.5 TGF-ß and integrins - a close relationship;467
10.2.6;5.2.6 Conclusions;471
10.2.7;5.2.7 Take-home message;471
10.3;5.3 Cancer-associated fibroblast integrins as therapeutic targets in the tumor microenvironment;482
10.3.1;5.3.1 Introduction;482
10.3.2;5.3.2 CAF Biology;482
10.3.3;5.3.3 Integrins on CAFs;483
10.3.4;5.3.4 Integrin function on CAF precursors;488
10.3.5;5.3.5 Integrin function in CAF differentiation;489
10.3.6;5.3.6 CAF integrins and tumor cell proliferation;491
10.3.7;5.3.7 Integrin function in CAF-promoted invasion and metastasis;491
10.3.8;5.3.8 Summary;494
10.4;5.4 Discoidin domain receptors: non-integrin collagen receptors on the move;501
10.4.1;5.4.1 Introduction;501
10.4.2;5.4.2 Collagen and collagen receptors;501
10.4.3;5.4.3 Discoidin domain receptor subfamily of receptor tyrosine kinases;504
10.4.4;5.4.4 Functions of DDRs;508
10.4.5;5.4.5 Conclusions;512
10.4.6;5.4.6 Take-home message;512
10.5;5.5 Syndecans as receptors for pericellular molecules;517
10.5.1;5.5.1 Introduction;517
10.5.2;5.5.2 Syndecans as cell surface ECM receptors;519
10.5.3;5.5.3 Syndecans as receptors mediating endocytosis;523
10.5.4;5.5.4 Syndecans as receptors for growth factors and chemokines;523
10.5.5;5.5.5 Perspective – specificity of syndecans and their signaling responses;527
10.5.6;5.5.6 Take-home message;528
10.6;5.6 CD44: a Sensor of tissue damage critical for restoring homeostasis;534
10.6.1;5.6.1 Introduction;534
10.6.2;5.6.2 CD44 structure and processing;535
10.6.3;5.6.3 Hyaluronan and other ligands of CD44;535
10.6.4;5.6.4 CD44-mediated signaling;536
10.6.5;5.6.5 CD44 function in mesenchymal stromal cells;537
10.6.6;5.6.6 CD44 function in leukocytes;541
10.6.7;5.6.7 Role of CD44 in the resolution of inflammation;542
10.6.8;5.6.8 CD44 in disease and as a potential therapeutic target;542
10.6.9;5.6.9 Concluding remarks;543
10.6.10;5.6.10 Take-home message;544
11;6 Collagen: insights into the folding, assembly and functions;549
11.1;6.1 Introduction;551
11.2;6.2 Trimerization domains in collagens: chain selection, folding initiation, and triple-helix stabilization;556
11.2.1;6.2.1 Introduction;556
11.2.2;6.2.2 Chain selection and trimerization;557
11.2.3;6.2.3 Trimerization domains and triple-helix folding and stabilization;563
11.2.4;6.2.4 Pathologies associated with trimerization domains;564
11.2.5;6.2.5 Future prospects and challenges;565
11.2.6;6.2.6 Take-home message;566
11.3;6.3 Structural basis of collagen missense mutations;571
11.3.1;6.3.1 Introduction: collagens and disease;571
11.3.2;6.3.2 Peptide models of collagen mutations;571
11.3.3;6.3.3 Computational analysis;578
11.3.4;6.3.4 Collagen mutations in a recombinant bacterial system;580
11.3.5;6.3.5 Summary and take-home message;585
11.4;6.4 Roles and regulation of BMP1/Tolloid-like proteinases: collagen/matrix assembly, growth factor activation, and beyond;589
11.4.1;6.4.1 Introduction;589
11.4.2;6.4.2 BMP1/Tolloid-like proteinases;589
11.4.3;6.4.3 Substrates;592
11.4.4;6.4.4 Endogenous regulators of activity;600
11.4.5;6.4.5 Meprins and matrix assembly;604
11.4.6;6.4.6 Conclusions and take-home message;605
11.5;6.5 Supramolecular assembly of type I collagen;612
11.5.1;6.5.1 Introduction;612
11.5.2;6.5.2 The multimodal fibrils: tendon, bone, and ligaments;613
11.5.3;6.5.3 The unimodal fibrils: cornea, sheaths, and blood vessels;617
11.5.4;6.5.4 Take-home message;621
11.6;6.6 Collagen interactomes: mapping functional domains and mutations on fibrillar and network-forming collagens;625
11.6.1;6.6.1 Collagen interactomes;625
11.6.2;6.6.2 Type I collagen interactome;626
11.6.3;6.6.3 Type IV collagen interactome;632
11.6.4;6.6.4 Type III collagen interactome;636
11.6.5;6.6.5 Type II collagen;637
11.6.6;6.6.6 Type X collagen;637
11.6.7;6.6.7 Future perspectives;638
11.6.8;6.6.8 Take-home message;638
11.7;6.7 Collagen-binding proteins;642
11.7.1;6.7.1 Introduction;642
11.7.2;6.7.2 Heat-shock protein 47;643
11.7.3;6.7.3 Pigment epithelium-derived factor;644
11.7.4;6.7.4 Fibronectin;645
11.7.5;6.7.5 Von Willebrand factor;646
11.7.6;6.7.6 Glycoprotein VI;646
11.7.7;6.7.7 Leukocyte-associated immunoglobulin-like receptor-1;647
11.7.8;6.7.8 Discoidin domain receptors (DDR);647
11.7.9;6.7.9 Secreted protein acidic and rich in cysteine;648
11.7.10;6.7.10 Take-home message;650
12;7 Emerging aspects in extracellular matrix pathobiology;653
12.1;7.1 Introduction;655
12.2;7.2 Extracellular matrix in breast cancer: permissive and restrictive influences emanating from the stroma;660
12.2.1;7.2.1 Introduction;660
12.2.2;7.2.2 The extracellular context in the mammary gland;660
12.2.3;7.2.3 The physical role of connective tissue stroma;663
12.2.4;7.2.4 The proteomic lesson;666
12.2.5;7.2.5 Concluding remarks;669
12.2.6;7.2.6 Challenges and future prospects;671
12.2.7;7.2.7 Take-home message;671
12.3;7.3 EMMPRIN/CD147: potential functions in tumor microenvironment and therapeutic target for human cancer;676
12.3.1;7.3.1 Introduction;676
12.3.2;7.3.2 Protease-inducing activity of EMMPRIN: role in tumor cell invasion;679
12.3.3;7.3.3 Role of EMMPRIN in myofibroblast differentiation;680
12.3.4;7.3.4 Role of EMMPRIN in angiogenesis;681
12.3.5;7.3.5 Shedding of EMMPRIN;682
12.3.6;7.3.6 EMMPRIN as a therapeutic target for human cancer;683
12.3.7;7.3.7 Take-home message;684
12.4;7.4 Implication of hyaluronidases in cancer growth, metastasis, diagnosis, and treatment;689
12.4.1;7.4.1 Introduction;689
12.4.2;7.4.2 Hyaluronidases in cancer;690
12.4.3;7.4.3 Regulation of hyaluronidase activity;693
12.4.4;7.4.4 Hyaluronidases and cell cycle progression;694
12.4.5;7.4.5 Anticancer properties of hyaluronidases;696
12.4.6;7.4.6 Further medical applications of hyaluronidases;698
12.4.7;7.4.7 Challenges and future prospects;699
12.4.8;7.4.8 Take-home message;699
12.5;7.5 Structure-function relationship of syndecan-1, with focus on nuclear translocation and tumor cell behavior;703
12.5.1;7.5.1 Syndecans;703
12.5.2;7.5.2 Structural organization;703
12.5.3;7.5.3 Functional domains and cellular interactions;704
12.5.4;7.5.4 Cellular distribution and nuclear translocation;706
12.5.5;7.5.5 Nuclear interactions;708
12.5.6;7.5.6 Syndecan-1 expression in normal tissues;710
12.5.7;7.5.7 Syndecan-1 in cancers;711
12.5.8;7.5.8 Syndecan expression affects tumor cell behavior;714
12.5.9;7.5.9 Potential for translation;716
12.5.10;7.5.10 Take-home message;718
12.6;7.6 Serglycin: a novel player in the terrain of neoplasia;727
12.6.1;7.6.1 Introduction;727
12.6.2;7.6.2 Expression of serglycin in malignancies;728
12.6.3;7.6.3 Regulation of serglycin gene expression;729
12.6.4;7.6.4 Functional importance of serglycin in malignancies;729
12.6.5;7.6.5 Serglycin regulates the secretion of proteolytic enzymes;732
12.6.6;7.6.6 Serglycin regulates the secretion and properties of inflammatory mediators;733
12.6.7;7.6.7 Take-home message;735
12.7;7.7 Quantifying cell-ECM pathobiology in 3D;739
12.7.1;7.7.1 Introduction;739
12.7.2;7.7.2 Importance of three-dimensional culture systems;739
12.7.3;7.7.3 Advancements in 3D quantification;742
12.7.4;7.7.4 Future directions;747
12.7.5;7.7.5 Take-home message;748
12.8;7.8 Diabetic foot infections;753
12.8.1;7.8.1 Introduction;753
12.8.2;7.8.2 Serological diagnosis of osteitis in foot infection in diabetes mellitus;758
12.8.3;7.8.3 Conclusion and summary;760
12.8.4;7.8.4 Take-home message;760
13;8 Targeting tumor microenvironment at the ECM level;767
13.1;8.1 Introduction;769
13.2;8.2 Targeting the tumor microenvironment in cancer progression;773
13.2.1;8.2.1 Targeting the tumor microenvironment;773
13.2.2;8.2.2 Cancer stem cells;778
13.2.3;8.2.3 Tumor angiogenesis: new concepts about the tumor microenvironment;781
13.2.4;8.2.4 CD44 in tumor biology;782
13.2.5;8.2.5 Take-home message;786
13.3;8.3 Growth factor signaling and extracellular matrix;791
13.3.1;8.3.1 Introduction;791
13.3.2;8.3.2 Interplay of growth factors and ECM;791
13.3.3;8.3.3 Growth factor signaling regulates ECM composition;794
13.3.4;8.3.4 Effect of ECM on growth factor action;799
13.3.5;8.3.5 Pharmacological Interventions;801
13.3.6;8.3.6 Take-home message;803
13.4;8.4 Targeting protein-glycan interactions at cell surface during EMT and hematogenous metastasis: consequences on tumor invasion and metastasis;813
13.4.1;8.4.1 Introduction;813
13.4.2;8.4.2 Tumor invasion and metastasis;815
13.4.3;8.4.3 Unique glycosaminoglycans from marine invertebrates and their potential antitumor activity;822
13.4.4;8.4.4 Challenges and future prospects;825
13.4.5;8.4.5 Take-home message;826
13.5;8.5 Pharmacological targeting of proteoglycans and metalloproteinases: an emerging aspect in cancer treatment;835
13.5.1;8.5.1 Introduction;835
13.5.2;8.5.2 The importance of targeting at ECM level in tumor progression;835
13.5.3;8.5.3 Pharmacological targeting of proteoglycans;836
13.5.4;8.5.4 Pharmacological targeting of matrix metalloproteinases;842
13.5.5;8.5.5 Pharmacological targeting of PGs/MMPs at the proteasome level;845
13.5.6;8.5.6 Concluding remarks;846
13.5.7;8.5.7 Take-home message;847
13.6;8.6 Targeting syndecan shedding in cancer;852
13.6.1;8.6.1 Introduction;852
13.6.2;8.6.2 Syndecan sheddases;853
13.6.3;8.6.3 Tissue inhibitors of metalloproteinases;854
13.6.4;8.6.4 Syndecan shedding and cancer;854
13.6.5;8.6.5 Future prospects;858
13.6.6;8.6.6 Take-home message;859
13.7;8.7 PG receptors with phosphatase action in cancer and angiogenesis;863
13.7.1;8.7.1 Introduction;863
13.7.2;8.7.2 Glycosylated transmembrane protein phosphatase receptors;865
13.7.3;8.7.3 RPTP-ß/.;867
13.7.4;8.7.4 Conclusions;870
13.7.5;8.7.5 Take-home message;870
13.8;8.8 Heparanase, a multifaceted protein involved in cancer, chronic inflammation, and kidney dysfunction;874
13.8.1;8.8.1 Introduction;874
13.8.2;8.8.2 Involvement of heparanase in cancer progression;878
13.8.3;8.8.3 Heparanase and inflammation;886
13.8.4;8.8.4 Heparanase and diabetic nephropathy;890
13.8.5;8.8.5 Challenges and future perspectives;892
13.8.6;8.8.6 Take-home message;893
13.9;8.9 Delivery systems targeting cancer at the level of ECM;905
13.9.1;8.9.1 Introduction;905
13.9.2;8.9.2 Targeting cancer;907
13.9.3;8.9.3 CD44-HA in tumor biology;910
13.9.4;8.9.4 Strategies that target CD44 to perturb HA-CD44 interaction in tumors;913
13.9.5;8.9.5 Take-home message;918
14;Index;923
