Purification and characterization of scatter factor.

Scatter factor is a fibroblast-derived protein which disrupts and scatters epithelial colonies and enhances the local movement of individual epithelial and endothelial cells. The factor purified from mouse fibroblasts by cation-exchange and reverse phase chromatography is a dimer of 57 kD and 30 kD protein subunits (A and B subunits), is active at picomolar concentrations and requires intact intra- and/or inter-chain disulphide bonds for activity. In serum-free conditioned medium the factor is highly aggregated but in the presence of high-salt buffers or protein denaturants elutes from gel filtration columns with an apparent Mr of approximately 50 kD. From a combination of molecular sieving and ultracentrifugation studies, a calculated Mr of 61.4 kD is obtained for native mouse scatter factor, a value which agrees well with the Mr estimates obtained by SDS-PAGE (62-67 kD). Mouse fibroblast scatter factor is a heparin-binding, basic protein (pI 8.5-9.5) which contains N-linked carbohydrates which are not, however, essential for activity. The factor has no metallo- or serine protease activity and there is no evidence so far that its junctional-breaking activity involves proteolytic cleavage of surface molecules on target cells. Scatter factor is either identical or closely related to hepatocyte growth factor/hepatopoietin A (a potent mitogen for rat hepatocytes recently purified from human and rabbit serum and rat platelets). The factor is thus an effector of mesenchymal-epithelial interactions which affects the movement or the growth of different epithelia.