Preface. 1. Introduction. 2. Homotypic and Heterotypic Cell Adhesion in Metastasis. 2.1 Release of malignant cells from the tumor mass: intercellular cohesion. 2.2 Malignant tumor cells in the blood stream: interactions with blood. 2.3 Adhesion to the target organ. 3. Motility, Deformability and Metastasis. 3.1 Motility and metastasis. 3.2 The role of active and passive deformability in invasion and resistance to shear stress forces in the blood stream. 4. ECM Degradation and Invasion. 4.1 Degradation. 4.2 Invasion. 5. The Role of Growth Interactions in Cancer Metastasis. 5.1 Methods to evaluate growth interactions in vitro. 5.2 Growth interactions in vivo. 6. Selection of Metastatic Variants. 6.1 Selection of organ-specific metastatic variants. 6.2 Selection of metastatic variants with enhanced or decreased metastatic abilities. 7. Genetic Tagging as a Mean to Study Tumor Progression or Metastasis-related Genes. 7.1 Clonal dominance in tumor progression. 7.2 Visualization of cancer metastasis. 7.3 Genes controlling the metastatic phenotype: use of gene tags to identify metastasis-related genes. 8. In Vivo Cancer Metastasis Assays. 8.1 Why study metastasis in vivo? 8.2 What defines an appropriate model of metastasis? 8.3 Cell lines. 8.4 Considerations regarding animals. 8.5 Site of injection. 8.6 Materials needed. 8.7 Spontaneous metastasis assay. 8.8 Experimental metastasis assay. 8.9 Enumeration of metastases. 8.10 Statistical considerations. 8.11 The influence of stress. 8.12 Concluding remarks. 9. Angiogenesis and Metastasis. 9.1 The corneal assay for angiogenesis. 9.2 The chick embryo chorioallantoic membrane assay. 9.3 Subcutaneous implant assay. References.
The book describes most of the methods that are currently used in metastasis research. Both in vivo and in vitro protocols are illustrated, so that the metastatic process can be either analysed as a whole, or single events addressed separately. Each method is described in the frame of the metastatic process, therefore its significance and its limitations in the context of metastasis are always taken into account. Whenever possible, several alternative procedures are reported per each experimental issue, so that the researcher can choose the one that better suits her/his needs and possibilities.
During the past 30 years a big effort has been made to elucidate the molecular mechanisms of cancer metastatis, the leading cause of death for cancer patients. A considerable number of assays have been set up, that can be used to address specific questions concerning the single metastatic steps, or can be applied to develop and test drugs specifically interfering with selected events during the metastatic spread. This book contains an exhaustive description of most of the methods and their rationale, that are currently used in metastatic research, both to analyse metastasis in its entirety (in vivo models), or to dissect the single steps of the metastatic process (in vitro assays).
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The Jake Gitlin Cancer Research Institute, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033-0850 USA
Friedrich Miescher Institute, Maulbeerstrasse 66, Basel, CH 4058 Switzerland
Friedrich Miescher Institute, Maulbeerstrasse 66, Basel, CH-4058 Switzerland