Conservation of epithelial cell phenotypes during hematogenous metastasis from mammary carcinomas.

The phenotypic heterogeneity of epithelial cells during hematogenous metastasis from primary mammary carcinomas of BALB/cfC3H mice was examined. Antisera to keratins were used in immunofluorescence assays to identify epithelial and myoepithelial cells. Both cell types were located in frozen sections of not only the primary lesions but also pulmonary metastases. Tumor cells disseminating to the lungs were recovered from the bloodstream of tumor-bearing mice with the use of a quantitative density gradient centrifugation procedure. Carcinoma cells were detected in the circulation of 62% of mice at the time of assay, but all tumors examined had released cells into the circulation at some point in their history. Epithelial cells and myoepithelial cells were detected simultaneously in 21% of mice, whereas other mice had only epithelial cells (16%) or myoepithelial cells (25%) in their circulation at the time of assay. Single cells and multicellular emboli of each cell type were disseminated, together with similar numbers of heterogeneous emboli containing both epithelial and myoepithelial cells. The evidence shows that the presence of both mammary epithelial and myoepithelial cells in pulmonary metastases from mouse mammary carcinomas can be accounted for by their hematogenous delivery as differentiated cells.