Altered Gene Expression in Tumor Metastasis: The nm23 Gene

Abstract

Tumor metastasis is a complex process involving tumor cell invasion, locomotion, intravasation and extravasation of the circulatory system, angiogenisis, colony formation, and avoidance of host immunological responses. Two premises have guided our investigation into the genetic influences on tumor invasion and metastasis. First, if the metastatic process is regulated, at least in part, by the activation and deactivation of specific genes, then the multiplicity of cell functions in metastasis dictates that many genes are involved. Second, the biochemical nature of molecules regulating and executing each of the tumor cell functions in metastatis is incompletely understood. Because of the tedious purification process, it is likely that many metastasis regulatory and effector compounds and the genes encoding them are presently unknown. Based on these premises, we initiated differential colony hybridization experiments to identify genes associated with the tumor invasion and metastatic process. This technique identifies genes either activated or deactivated between tumor cells of low and high metastatic potential. It can therefore identify metastasis-related genes in advance of conventional biochemical purification and DNA cloning. This paper describes the identification and characterization of one such gene, nm23.