Basic mechanisms of metastasis.

Metastatic disease is responsible for the majority of deaths caused by cancer. The process of metastasis is an orderly, stepwise process that results in the selection of cells that possess the capability to establish viable metastases. These cells must be locally invasive and be able to survive the physical traumas of dissemination and normal host defenses. Once metastatic cells have been arrested in a capillary bed, they must be able to invade the host organ parenchyma and survive in that milieu. Studies in a number of model systems have documented the phenotypic alterations in cells that have "metastatic potential." These differences may stem from normal tumor cell heterogeneity and surprisingly reflect only minor differences in gene expression. The role of activated oncogenes in metastasis is unclear, but a number of laboratories have documented that transfection with activated Ha-Ras results in increased metastatic potential. An increased understanding of the genetic basis of metastatic potential may suggest new directions for intervening in this deadly process.