On the genesis and regulation of cellular heterogeneity in malignant tumors.

The growing body of evidence showing that malignant tumors are heterogeneous and contain diverse subpopulations of cells with different metastatic abilities is reviewed. The factors that may influence the evolution of cellular diversity at different stages in the progression of malignant neoplasms are discussed. Particular emphasis is given to the possibility that interactions occurring between the constituent subpopulations of a malignant tumor may influence the rate at which new variant subpopulations emerge. Metastatic heterogeneity poses significant problems for experimental efforts to identify the cellular features that correlate with metastatic behavior and for the therapy of metastatic disease.