PATTERNS OF DIFFERENTIATION IN EXTRAOSSEOUS EWINGS-SARCOMA CELLS - ANIN-VITRO STUDY

Background. In vitro, tissue culture-associated differentiation assays have facilitated the identification of multiple tumor-cell types. Met hods. We have investigated the capability of differentiation of three extraosseous Ewing's sarcoma cell lines toward a neural and muscular d irection by in vitro stimulation with dibutyryl cyclic adenosinemonoph osphate (db cAMP) and 5-azacytidine, respectively. Results. Elongation of cytoplasmic processes and increase of neural markers chromogranin, S-100 protein, and glial fibrillary acidic protein were observed afte r db cAMP treatment of these lines and neurosecretory granules as well as myelin figures were demonstrated ultrastructurally. These results support the existence of several pathways of neural differentiation in vitro-neuroblastic, Schwannian, and central glial-in stages of matura tion more advanced than those previously reported in Ewing's sarcoma o f bone. The cell lines showed no definitive myoblastic differentiation after 5-azacytidine treatment. Conclusions. These data suggest that t hese three extraosseous Ewing's sarcoma cell lines configurate a heter ogeneous group of tumors with respect to capability of differentiation into the neural lineage, arrested at more advanced stages of neural c rest development than Ewing's sarcoma of bone and without capability o f myoblastic differentiation with 5-azacytidine.