Genetic regulation of metastatic progression.

Metastasis is a complex process which results in the growth of tumor cells at sites distant from the primary neoplasm. It is likely that many of the large number of biological changes associated with metastatic ability are controlled through alterations in the expression of a relatively small number of key genes usually referred to as cellular oncogenes and tumor suppressor genes. These genes are normally required for the regulation of growth-related processes in the cell, and alterations through mutations and/or expression are important in establishing metastatic properties of malignant cells. In this article, we review evidence indicating that oncogenes play an important role in metastatic spread, and we have placed emphasis on studies with the ras oncogenes. Metastatic progression is dependent upon an accumulation of multiple genetic changes in malignant cells. Therefore, we have also briefly addressed the related questions of altered growth factor regulation, and the cooperative interactions observed between dominantly acting oncogenes and between these genes, and tumor suppressor genes.