CONTENTS

Preface  viii
1. Matrix Metalloproteinases in Cancer Cell Invasion .. 1
Niina Reunanen and Veli-Matti Kähäri
Abstract . 1
Matrix Metalloproteinases  1
Regulation of MMP Activity .. 7
MMPs in Tumor Growth and Invasion . 9
TIMPs in Tumor Growth and Invasion . 10
2. Integrins in Cancer Cell Invasion  20
Pekka Koistinen and Jyrki Heino
Integrins . 20
Integrins as Extracellular Matrix Receptors  20
Integrin Structure .. 21
Integrins in Human Cancer .. 21
Altered Integrin Expression in Three Common Types
of Human Cancer  22
Integrins and Invasion . 28
Integrins and MMPs  29
Cellular Signals Between Integrins and MMP Genes  29
Integrins as MMP Receptors  32
Acknowledgments . 33
3. Keratinocyte Interactions with Fibronectin During Wound Healing  42
H. Larjava, L. Koivisto and L. Häkkinen
Abstract .. 42
Reepithelialization: A Controlled Migration/Invasion
of Keratinocytes . 42
Keratinocyte Invasion into the Clot .. 43
Cell Adhesive Sites of Fibronectin . 46
Biological Functions of Fibronectin Matricryptins  49
Fibronectin Matrix Assembly and Cross-Linking to Fibrin  49
Fibronectin Receptor Integrin Expression During Re-Epithelialization:
α5β1 Integrin  51
Function of αvβ6 Integrin  55
Role of αvβ6 Integrin in Malignant Transformation of Keratinocytes . 56
How do Keratinocytes Migrate on a Composite Matrix?  57
Conclusions .. 58
Acknowledgments . 58
4. Matrix Metalloproteinases and Cell Migration in the Development
of Cardiovascular Disease  65
Sarah J. George, Andrew C. Newby and Andrew H. Baker
Extracellular Matrix Composition of the Blood Vessel Wall . 65
Extracellular Matrix Disruption in Vessel Wall Remodelling  67
Matrix Metalloproteinases . 69
MMPs and Cardiovascular Disease  72
MMPs and the Development of Atherosclerosis . 73
MMPs and Acute Vascular Injury . 77
MMPs and In Vitro Studies . 77
Concluding Remarks  81
5. Cancer Invasion-Related Genes  89
Anja Bosserhoff and Reinhard Buettner
Introduction . 89
Proteases . 89
Non-Proteolytic Enzymes .. 90
Cell-Cell Adhesion Molecules .. 91
Cell-Matrix Adhesion Molecules  92
Matrix Molecules .. 93
Growth Factors .. 93
Cytokines .. 95
Intracellular Molecules of Signal Transduction Pathways .. 96
Cytoskeleton  98
Recently Identified Genes with Complex Functions . 98
Discussion .. 101
Terms  102
6. Common Mechanistic Features in Cell-Extracellular Matrix
Interactions Regulating Neurite Outgrowth
and Tumor Cell Invasion . 108
Henri J. Huttunen and Heikki Rauvala
Summary . 108
Integrin-Matrix Interactions in Neurite Outgrowth
and Invasive Cell Migration . 109
TSR (ThrombospondinType 1) Superfamily Proteins .. 111
Syndecans  113
Interaction of Extracellular Matrix Molecules
with the Immunoglobulin Superfamily Proteins . 114
Proteolytic Mechanisms in the Cell-Matrix Contacts . 115
Conclusions and Future Prospects .. 117
7. Emmprin (CD147), a Tumor Cell Surface Inducer of Matrix
Metalloproteinase Production  121
Bryan P. Toole
Introduction .. 121
Tumor Cell Emmprin Stimulates Fibroblast Production of MMPs  121
Autocrine Action of Emmprin Promotes Tumor Cell Invasiveness . 122
Emmprin Docks MMP-1 on the Tumor Cell Surface .. 123
Emmprin Promotes Tumor Growth and Invasion in Vivo . 123
The Functions of Emmprin are Diverse 124
Conclusions  124
8. The Plasminogen Activation System in Cell Invasion  128
M. Patrizia Stoppelli
Abstract  128
Introduction .. 128
Plasminogen and Plasminogen Activators  129
Plasminogen Activator Inhibitors  131
Plasminogen Activator Receptors . 132
Cell-surface Associated Plasminogen Activation  133
Biological Role of the uPA/uPA Receptor System  134
Plasminogen Activators and Tissue Remodeling .. 137
Plasminogen Activators and Invasion in Animal Models .. 137
Plasminogen Activators and Human Tumors  139
Conclusions and Perspectives  141
9. Influence of Cell-Extracellular Matrix Interactions on Keratinocyte
Behavior During Repair  148
Brian K. Pilcher, Jonathan C.R. Jones and William C. Parks
Introduction .. 148
Type I Collagen, Collagenase-1, and Keratinocyte Migration  150
Laminin Effects on Keratinocyte Behavior Upon Completion
of Reepithelialization  156
Concluding Remarks . 159
10. Matrix Metalloproteinases
and their Inhibitors in Clinical Oncology . 163
Taina Turpeenniemi-Hujanen
Abstract  163
Metalloproteinase System in Cancer .. 163
Measuring MMPs or TIMPs in Clinical Samples  164
MMPs in Breast Carcinoma .. 165
Metalloproteinases and Their Inhibitors in Urological Cancers  165
MMPs in Melanoma . 166
Markers of Matrix Degradation in Lung Carcinoma . 167
MMPs and their Inhibitors in Gastrointestinal Cancers  167
MMPs in Brain Neoplasias . 167
MMPs in Gynecological Malignancies . 168
Hematological Malignancies .. 169
The Role of MMPs in Bone Metastasis  169
Clinical Value of TIMPs . 169
Index .. 177