The overall objective of this research is to understand how normal tissue cells and cancer cells move within organisms. The emphasis is on: (1) the mechanism of cell locomotion within both embryos and adults, particularly during directional morphogenetic movements and wound closure, and (2) the mechanism of locomotion of invasive cancer cells--how they make contact with each other, with normal tissue cells, and with various substrata, and how this behavior relates to the acquisition of invasiveness. These two lines of emphasis are both concerned with the properties that make for cell locomotion: adhesion to the substratum (whether it consists of other cells or of extracellular matrix), protrusions of the cell surface, detachment, and retraction of the trailing edge, cell surface flow and plasma membrane assembly, cytoplasmic flow, microfilaments, and cytoplasmic contractility, microtubules and cytoplasmic viscosity, and contact inhibitory relations between cells. The principal techniques that will be utilized are cell culture, high-resolution Nomarski interference, phase contrast and interference reflection microscopy, time-lapse cinemicrography, transmission and scanning electron microscopy, micromanipulation, drug inhibition of microtubule assembly, contractility, and energy metabolism and labeling of contractile proteins with immunofluorescent antibodies. (A)
