The central theme of this research is the investigation, in in vitro systems and in an appropriate experimental animal tumor model, of the cell differentiation characteristics of tumors of the central and peripheral nervous systems. Of special importance in this regard are the human embryonal CNS tumors, about which more information is needed on their biology and differentiation potential. The neuroepithelial component of a transplantable mouse testicular teratoma (OTT-6050) and of its enriched fractions obtained by dissociation and centrifugal elutriation, an experimental system which permits the study of the entire range of divergent central neuroepithelial differentiation (neuronal and glial), from its earliest to its most mature stages, serves as the animal tumor model. Three approaches are utilized. 1) The organ culture system a) for the sequential in vitro study of morphologic and immunomorphologic differentiation, and b) for the determination of cell cycle kinetics and the measurement of the growth fraction developing in the 'steady state' of tumor growth in this system. Such an in vitro approach is opening new avenues in the exploration of human CNS tumor cell lines (medulloblastoma, giant-cell glioblastoma, retinoblastoma) in regard to their capacity for differentiation. 2) The expression of structural and non-structural markers of differentiation, including intermediate filament proteins (glial, neuronal), enzymatic cytoplasmic proteins (neuron-specific enolase), and cell surface membrane antigens. The recognition, by monoclonal antibodies, of surface antigens shared by the immune and nervous systems is providing new immunomorphologic tools that are important for the identification of neoplastic cells of the CNS and PNS. 3) A novel line of research is the determination and relative measurement of biogenic amines by high sensitivity microspectrofluorometry in the neuroepithelial cell populations of the OTT-6050 teratoma and its fractions, and in human embryonal CNS tumor cells and their explants, including some of their cell lines. The role of biogenic amines in regulating neural development suggests that they may be important in modulating differentiation in CNS and PNS tumors. The differentiation potential of these tumors provides an alternative direction in the therapeutic strategies to be considered in this form of cancer.
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