) The hypothesis that cellular locomotion and directed migration is a key component underlying invasive behavior has led to deeper investigation into the molecular events underlying motility and metastasis, the topic of this proposed meeting. The recent surge of discoveries into the molecular mechanisms regulating cellular migration has provided new avenues for research. Opportunities now exist to solve the following major puzzles: a) Tracing of a complete motility-regulating signal transduction pathway from the cell surface receptor to the cell pseudopod machinery; b) Explaining how sequential integration of cytoskeletal focal o r g anization, pseudopod protrusion, adhesion, de-adhesion, and matrix interactions can result in sustained locomotion, and (c) Defining the genetic events in tumor progression, including oncogene activation and suppressor de-activation, which drive the emergence of the motility. New cytokines, receptors, and cell surface enzymes have been identified which differentially stimulate or inhibit migration of tumor cells, epithelial cells, endothelial cells, stromal cells and immune cells. Membrane ion channels and portions of signal transduction pathways have been linked to individual components of motility: cell spreading, lamellopodial and pseudopodial protrusion, and focal contact formation. The structural domains of proteinases and their inhibitors which regulate motility and invasion within the extracellular matrix have been identified. Inhibitors of cell motility and invasion have been shown to block angiogenesis and to suppress tumor growth and metastasis in animal models. Thus, the field is poised to make great strides in understanding how motility, both physiological and malignant, is regulated and how to use this knowledge to drive new diagnostic, therapeutic, and prognostic endeavors. The goals of the meeting will be to develop a critical mass of new ideas, model systems, and observations to generate solutions to these puzzles; to resolve controversies in the field as a means to stimulate new hypotheses; and, to explore translational applications to disease diagnosis and treatment based upon these advances in the field of motility and metastasis.
