Biology of metastasis

The acquisition by tumor cells of the ability to metastasize is the critical event in the clinical course of most human neoplastic disease. While metastasis plays a pivotal role in the ultimate success or failure of therapy, it is in fact a result of a more insidious malignant process termed tumor progression. It is the progression of tumors from a less to a more malignant phenotype that results in tumor heterogeneity and the selection of cells with a more malignant (metastatic) phenotype. The development of metastases is thus integrally related to the mechanisms of tumor progression, which in turn is likely due to the instability of the tumor cell genome. The authors' thesis is that metastatic tumor cells are a selected population derived from a heterogenous parent tumor which contains many clones with different phenotypes. This discussion will, therefore, address the role of tumor genomic instability as a basis for the selection of metastatic cells. Cancer 58:550‐553, 1986.