Abstract

Tumor‐cell diversification mechanisms insure that malignant neoplasms contain diversified tumor‐cell subpopulations. Because of the instability of tumor cell phenotypes, some malignant cells will evolve with the most favorable properties for their progression to highly metastatic cells. The rates of cellular phenotypic diversification vary greatly among different tumors, and they are probably modulated, in part, by genetic and chromosome defects and by epigenetic events that may vary widely depending upon the nature of the tumor cells and their microenvironments. As tumor diversification and selection proceed, the most malignant cell subpopulations may eventually become dominant and gradually lose their microenvironmental responsiveness. Tumor‐cell diversification mechanisms may be similar or identical to normal, developmentally regulated diversification mechanisms that are used during embryonic cell diversification and differentiation.