Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera-2. Differentiation in vivo and in vitro.
We have derived and characterized single cell clones from a xenograft tumor of the teratocarcinoma cell line Tera-2. Isozyme and chromosomal analyses confirmed their common origin. When cultures of the clones were maintained at a high cell density, many cells exhibited a morphology and cell surface antigen phenotype typical of human embryonal carcinoma cells. These features included a high nucleo-cytoplasmic ratio, prominent nucleoli, and the expression of the globoseries glycolipid antigen SSEA-3. In addition, other cells, in many respects resembling these typical embryonal carcinoma cells, were distinguished by a marked tendency to accumulate cytoplasmic glycogen. Similar cells, together with more differentiated cells, were seen in low passage cultures of Tera-2 itself. When the clones were grown at a low cell density many cells assumed a larger, flatter shape, a few with multiple nucleoli. Also, the fucosylated lactosamine antigen SSEA-1 appeared on some cells, whereas expression of SSEA-3 and HLA-A,B,C tended to be reduced. Often the synthesis of fibronectin was increased. However, no obvious cytoplasmic differentiation was seen upon ultrastructural examination, and synthesis of human chorionic gonadotropin, alpha-fetoprotein, and laminin was not detected. In contrast to the limited spontaneous changes seen in culture, marked differentiation occurred in tumors obtained following injection of the cells into athymic (nu/nu) mice. In additional to embryonal carcinoma cells, these tumors contained a variety of somatic tissues that included glandular structures, possibly related to the primitive gut, and neural elements. These cell lines derived from Tera-2 constitute the first example of clonal human embryonal carcinoma cells, adapted to growth in vitro, that have retained the capacity for differentiation into diverse somatic tissues.
D000818:Animals; D000954:Antigens, Surface; D002460:Cell Line; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002999:Clone Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010641:Phenotype; D013724:Teratoma / Q000473:pathology / Q000648:ultrastructure*; D014183:Transplantation, Heterologous
D000954:Antigens, Surface