Dynamic heterogeneity and metastasis.

Parallel clonal populations grown to small defined sizes were used to quantitate rates of generation of metastatic cells. In murine KHT fibrosarcoma and B16 melanoma lines, metastatic cells are generated at effective rates of 10(-5) per cell per generation, or greater. These variant cells are unstable, and are apparently lost at very high rates. It thus appears that metastases could arise from unstable variants, and that rapid rates of change in some phenotypes may be an important feature of malignant progression. We have called such rapid variations dynamic heterogeneity. This may be a useful concept for further investigating aspects of tumor heterogeneity.