PLURIPOTENT EMBRYONAL CARCINOMA CLONES DERIVED FROM THE HUMAN TERATOCARCINOMA CELL-LINE TERA-2 - DIFFERENTIATION INVIVO AND INVITRO

  • 1 January 1984
    • journal article
    • research article
    • Vol. 50  (2) , 147-162
Abstract
Single cell clones from a xenograft tumor of the [human] teratocarcinoma cell line Tera-2 were derived and characterized. Isozyme and chromosomal analyses confirmed their common origin. When cultures of 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. 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. 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 cell 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 1st example of clonal human embryonal carcinoma cells, adapted to growth in vitro, that have retained the capacity for differentiation into diverse somatic tissues.