PERSPECTIVES ON CLASSIC ARTICLES: Metastasis Suppressor Genes

Extract

Historical Perspective

The metastasis suppressor gene field was launched in 1988 with the publication of an article in JNCI identifying nm23 (1). Despite the devastating consequences of tumor metastasis, little of its molecular regulation was known in 1988. Most studies at that time focused on the acquisition of traits, principally those involved in invasion. The instability of metastatic cell lines in terms of their behavior, gene expression patterns, and karyotypic abnormalities was thought to preclude the existence of consistent underlying molecular events. Genes up- or down-regulated in metastasis were identified almost exclusively in rodent model systems. We took a different approach and compared seven cell lines derived from a single murine K-1735 melanoma using differential colony hybridization (1). All of the cell lines formed primary tumors on intravenous injection into syngeneic and nude mice, but they varied widely in metastatic potential. Differential colony hybridization identified one cDNA, nm23, whose expression was quantitatively reduced in five highly metastatic cell lines as compared with two related, less metastatic cell lines. A similar pattern was observed in an independent model system, NMU-induced rat mammary carcinomas.