DIFFERENTIATION OF A EWINGS-SARCOMA CELL-LINE TOWARDS NEURAL AND MESENCHYMAL CELL LINEAGES

Two different pathways of differentiation were investigated in Ewing's sarcoma (ES) cell line, designated CADO-ES1, which has been establish ed in our laboratory. This cell line was induced to differentiate and display a neural phenotype when treated with dibutyryl cyclic adenosin e monophosphate or when cultured in serum-free medium (HB101). In thes e in vitro differentiation studies, two different phenotypes were demo nstrated by light and electron microscopy. One phenotype, present in a major portion of the cell population, had long neurites in which micr otubules were ultrastructurally demonstrated. The other one, present i n a minor portion of the cell population, consisted of flat cells with many short processes. After differentiation in serum-free medium, tum origenicity in nude mice or colony-forming efficiency in soft agar was strongly depressed. In the cells, N-myc, c=fos and c-src genes were n ot amplified, and although c-myc was amplified by up to 2-fold, depend ing on the culture conditions, this appeared to be unrelated to the ch anges of phenotype. When tumor cells were transplanted into nude mice, cartilage was formed. The cartilage was immunoreactive with the antib ody for HLA-ABC, indicating that it was derived from the tumor cells, not from mouse tissue.