The experimental and clinical implications of cellular heterogeneity in malignant tumors.

The growing body of evidence showing that malignant tumors are heterogeneous and contain diverse subpopulations of tumor cells is reviewed, with particular emphasis being given to the presence of tumor-cell subpopulations with differing metastatic properties. The factors that may influence the evolution of cellular diversity at different stages in the progression of malignant neoplasms are discussed. Emphasis is given to the possibility that interactions occurring amongst 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 features unique to metastatic cells and also for the therapy of metastatic disease.