Characterization of metastatic heterogeneity among subpopulations of a single mouse mammary tumor: heterogeneity in phenotypic stability.

The frequency of metastasis formed by tumor cells injected into lateral tail veins, mammary fatpads, or the subcutis are described for eight subpopulations of a single, spontaneously arising BALB/cfC3H mouse mammary tumor. These subpopulations display a spectrum of metastatic behavior from all three injection sites. The proportion of animals with metastases does not depend upon the site of primary tumor growth (i.e., mammary fatpad versus subcutis). One subpopulation can grow as lung nodules after intravenous injection but is only poorly metastatic from subcutaneous or fatpad implants. Heterogeneity among the subpopulations in the stability of the metastatic phenotype is evident. Although most of the subpopulations and their clones remained stable for periods of 2-5 years, one subpopulation rapidly lost metastatic ability within 3 months and another gradually became more metastatic over 2 years.