The aim of this research is to analyze the activity of retinoids (vitamin A analogues) on human tumor cell invasion in an in vitro model system. The in vitro quantitative test of cell invasiveness is based on findings that metastatic tumor cells penetrate and degrade the extracellular matrix of devitalized human amnion with its associated basement membrane. The biological response that is measured is of significance, relating directly to a specific stage in metastasis, i.e. tumor cell penetration of extracellular matrix barriers. A series of synthetic and natural retinoids will be evaluated in the in vitro invasion assay for their effect on invasiveness of human tumor cells, and on activity of enzymes known to act in basement membrane degradation. The usefulness of the in vitro invasion assay of the biological activity of retinoids will be evaluated in terms of end points that can be measured in a reproducible and quantitative doseresponsive manner. The study of retinoid effects on in vitro invasion by human tumor cells may provide a useful approach to investigation in two major areas of cancer research: (1) the exploration of the molecular mechanism of retinoid antinvasive activity in vitro to delineate the essential step(s) in cancer cell metastasis; and (2) the screening of new retinoids as well as other chemicals which might be useful for prevention or treatment of cancer in man.