Attempts to Understand Metastasis Formation II: Regulatory Factors

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 ot 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 tnetastatic cascade, proteolysis and alterations in adhesive functions are the most obvious and thus one of the most thoroughly investigated processes.