CD30 AND ITS LIGAND - POSSIBLE ROLE IN REGULATION OF TERATOMA STEM-CELLS

Like the oocyte, the cells of the early embryo, and primordial germ ce lls, human teratocarcinoma stem cells are pluripotent, capable of givi ng rise to a wide range of somatic and extraembryonic tissues. Growth factors which regulate the growth of multipotent stem cells in the mou se have been identified, but none of these have been shown conclusivel y to have similar effects on human or primate multipotent stem cells. CD30 is a member of the tumour necrosis factor receptor superfamily wi th a restricted pattern of tissue distribution, limited to immune cell s, decidual tissue, and human embryonal carcinoma: in common with othe r embryonal carcinoma markers, CD30 is found in foci of cells in a sub -population of seminomas. CD30 ligand is a transmembrane protein, stru cturally related to tumour necrosis superfamily members TNF alpha,, TN F beta, and CD40. CD30 ligand is expressed by T and B lymphocytes, mac rophages, and a variety of normal haematopoietic cells and tumours der ived from them, and exerts pleiotropic effects on normal and malignant lymphoid cells, including death, differentiation, or cell division. S tudies on cultured cell lines derived from human embryonal carcinomas and yolk sac carcinomas confirm CD30 expression in the former but not the latter, and show that CD30 expression is down-regulated during ste m cell differentiation in vitro. Transcripts for CD30 ligand are found at highest levels in yolk sac carcinoma cell lines, but are also foun d in embryonal carcinoma. CD30 ligand protein is detected in yolk sac carcinoma and nullipotent embryonal carcinoma cell lines. Exogenous CD 30 ligand has no effect on multipotent human stem cell growth in vitro . However, the receptor-ligand pair may function in autocrine regulati on of embryonal carcinoma stem cells. CD30 and its ligand are candidat e stem cell identity factors, juxtacrine regulators whose sole functio n is to identify a cell's position in a developmental hierarchy.