In metastasis, tumor cells disseminate from the primary lesion and home to secondary organs where they may remain dormant for a long time. Metastasis formation is still the most feared manifestation for tumor patients and clinicians. Although improvements have been made concerning earlier detection and specific therapy, most of the cancer patients still die of distant metastases. The pu-rpose of these three volumes is to review the recent progress in molecular metas tasis research and to attempt to further understand the biol ogy of this multifocal process. With respect to present day molecular biology, the pioneers of metastasis research established the basic concepts of metasta sis formation in the 1970s and 1980s, namely, clonal selection of metastatic cells, heterogeneity of metastatic subpopulations, organ specificity of metastasis and the importance of angio genesis (Fidler, Kripke, Nicolson, Folkman and others). In the 1980s and 1990s, several of the molecules involved were identified and their network interactions elucidated. These three volumes of Current Topics in Microbiology and Immuno logy compile the most recent developments on these meta stasis-related molecules; their interactions, regulation, and ways to interfere with their action. It became evident that metastasis-related molecules are confined to distinct cellular compartments, such as the extracellular space, the cell membrane, the cytoplasmic signalling network, and the nuclear regulatory system. For the complex metastatic cascade, proteolysis and alterations in adhesive functions are the most obvious and thus one of the most thoroughly investigated processes.

Within the last decade the molecular biology of tumor models has revealed the identification of several metastasis- related molecules. These volumes attempt to review the most recent approaches of their mechanisms, regulation and way to treat their malignant alterations. The first volume covers the presentation of proteases and inhibitors and their role in invasion of tumor cells, also cell adhesion molecules and their interaction with the extracellular matrix. In the second volume the regulation of tumor progression and angiogenesis by cytokines, growth factors and motility factors is outlined. The third volume deals with detection of micrometastases and therapeutic approaches, such as immunotherapy, gene therapy, chemotherapy and surgical strategies to combat metastatic spread.

In metastasis, tumor cells disseminate from the primary lesion and home to secondary organs where they may remain dormant for a long time. Metastasis formation is still the most feared manifestation for tumor patients and clinicians. Although improvements have been made concerning earlier detection and specific therapy, most of the cancer patients still die of distant metastases. The purpose of these three volumes is to review the recent progress in molecular metas tasis research and to attempt to further understand the biol ogy of this multifocal process. With respect to present day molecular biology, the pioneers of metastasis research established the basic concepts of metasta sis formation in the 1970s and 1980s, namely, clonal selection of metastatic cells, heterogeneity of metastatic subpopulations, organ specificity of metastasis and the importance of angio genesis (Fidler, Kripke, Nicolson, Folkman and others). In the 1980s and 1990s, several of the molecules involved were identified and their network interactions elucidated. These three volumes of Current Topics in Microbiology and Immuno logy compile the most recent developments on these meta stasis-related molecules; their interactions, regulation, and ways to interfere with their action. It became evident that metastasis-related molecules are confined to distinct cellular compartments, such as the extracellular space, the cell membrane, the cytoplasmic signalling network, and the nuclear regulatory system. For the complex metastatic cascade, proteolysis and alterations in adhesive functions are the most obvious and thus one of the most thoroughly investigated processes.

An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.

In Volume I, Analysis of Cells and Tissues, we presented a range of protocols aimed at mapping and analyzing the expression of various molecules of pot- tial interest in metastasis research and for examining their production at the genetic level. In this second volume of metastasis research protocols, we move to the level of living cells and tissues and present methodologies applicable to examining metastatic behavior in vitro and in whole animal models. The methods described in the first section of this volume concentrate on the separation of cell lines with high and low metastatic potential, including the genetic modification of cell lines. The assay systems to test defined aspects of the metastatic cascade are then described in Part II and include cell migration assays, assays for matrix degrading enzymes, basement membrane degrading assays, adhesion assays, and assays of angiogenesis. The role of the specific elements of the metastatic cascade assayed in each of these systems in turn must of course be put into perspective relative to their roles in entire living organisms.