Lack of production of myoepithelial variants by cloned epithelial cell lines derived from the TMT-081 metastasizing rat mammary tumor.

ABSTRACT

A series of cell lines was isolated from the metastasizing rat mammary tumor cell strain TMT-081. MS by single-cell cloning. Feeder cells were required for development of single tumor cells into clonal colonies. The rate, pattern, and incidence of metastases following injection of cells into the mammary fat pads of syngeneic rats were relatively similar for the various cell lines, with dissemination to the lungs and axillary and paraaortic lymph nodes. When a representative cell line termed Rama 800 was subcloned, one subline was nontumorigenic, and another gave a lower incidence of lung metastases, but the remainder had similar in vivo properties to the parental Rama 800 cells. The metastatic properties of Rama 800 cells were not affected by passage in vitro through 60 cell generations. No production of myoepithelial-like variants from Rama 800 cells was observed at the ultrastructural level. Antisera to keratin, actin, laminin, and fibronectin, which normally stain myoepithelial cells and basement membrane, failed to stain Rama 800 cells, either in cultures or in tumor sections. Heterogeneous staining of Rama 800 tumor cells with antiserum to epithelial cell-specific milk fat globule membrane antigens was seen in tumor sections but not in culture. Abundant microvilli and membrane blebs were observed on the surface of cultured Rama 800 cells, but no lumen formation, desmosomes, or tonofilaments were seen, either in vivo or in vitro. The results suggest that the metastatic epithelial-derived cell lines lack the ability to express features of myoepithelial cells, in contrast to cell lines isolated previously from nonmetastasizing rat mammary tumors.