Increased metastatic ability and bone formation of a mammary adenocarcinoma in vivo after in vitro passaging.

On in vitro passaging of the rat mammary adenocarcinoma R3230AC cell line, phenotypic changes occurred that were expressed in vivo. The histology of this mammary adenocarcinoma changed to a fibrosarcoma and then to an osteosarcoma. The overall population of early passaged cells consisted of a mixture of predominantly epithelial-like cells and few fibroblast-like cells; however, later passaged cells consisted more of the latter type. Along with the changes in histology, the tumor line also became highly metastatic in animals after in vitro passaging. The etiology of these phenotypic changes was not determined. Cytogenetic studies revealed chromosome changes in cells of later passages. Cells of 90 or greater passages that produced bone tumors were found to have fewer chromosomes and a metacentric marker isochromosome. In this report a correlation is made between the aberrant change in histology, increased metastatic ability and the presence of a marker chromosome of the R3230AC tumor.