Extracellular Matrix: Pathobiology and Signaling

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