[Scatter factor and cell motility]

Cell dispersion and motility are thought to be important steps in the invasion of tumor cells. The molecular mechanisms responsible for the induction of cell dispersion and motility remain unclear. Several factors affecting cell motility have been discovered. Among them, scatter factor (SF), a mesenchymal cell-derived protein, dissociates epithelial cell colonies into individual cells and stimulates the migration of epithelial cells. Purified SF promotes the invasiveness into collagen matrices of a number of human carcinoma cell lines, suggesting that SF is involved in the invasion of tumor cells. Recently, SF has been found to be identical to hepatocyte growth factor. Moreover, the c-met proto-oncogene product (the c-met protein) possessing a tyrosine kinase domain was identified as a receptor for SF. Three possible mechanisms have been postulated in which a tumor cell might increase its invasive potential through enhanced motility via SF and its receptor. First, in a cell already expressing the c-met protein, an unexpressed SF gene might be activated, leading to synthesis and secretion of the factor which could then initiate active motility in an autocrine fashion. Second, the tumor cell expressing the c-met protein may release a factor that affects surrounding mesenchymal cells, promotes synthesis and release of SF. The tumor cell would be stimulated in a paracrine fashion. Finally, the tumor cell may be exposed to SF already released by surrounding cells but may not be able to respond because it is partially or completely deficient in the c-met protein. Induction and increased expression of the c-met gene would result in the invasive phenotype of the tumor cell. Studies on these possible mechanisms will be required to elucidate the involvement of SF in the invasion of tumor cells.