Oncogene transformation and the metastatic phenotype.

In this review, we first discuss some of the experimental parameters that need to be considered in assessing the contribution of various oncogenes to tumor metastasis. We discuss the requirement for a number of in vivo assays to measure different aspects of metastatic ability and we describe a novel metastasis assay, which we have developed, in the naturally immune-deficient chick embryo. Other factors capable of influencing the effects of oncogenes in experimental studies of metastasis, including oncogene activation and the differentiated status of the recipient cell, are also examined. We present some of our experimental results analyzing the ability of two oncogenes, src and ras, to convert cells to a metastatic phenotype. We speculate that a major mechanism by which some oncogenes promote metastatic ability is by subverting a signal transduction process, resulting in activation of a set of genes, some of which appear to promote metastatic ability. Finally, we discuss the need for additional information on the contributions of oncogenes to tumor progression and metastasis in both experimental systems as well as in clinical tumors.