Retinoblastoma cells in tissue culture

This review summarizes and discusses research on retinoblastoma (Rb) cells in tissue culture. Retinoblastoma is an intraocular tumor of early childhood which is believed to originate from the primitive multipotential neuroectoderm of the optic cup region. The application of tissue culture techniques to the study of Rb cells permits detailed studies of the biology of this tumor. Classic studies have primarily focussed on growth and metastatic potential of Rb cells. Y-79 Rb cells, for example, have a short doubling time in vitro as well as aggressively growing in the anterior chambers of athymic 'nude' mice. Such active growth may result from secretion of a Retinoblastoma Derived Growth Factor (RDGF) by the cells. Several natural agents have now been shown to halt Rb cell growth in vitro. Among these are the fatty acid, butyrate, and two retinoids: retinol and retinoic acid. Interestingly, the retinoids have different mechanisms of action. Cultured Y-79 and WERI cells appear to be multipotential in that they exhibit both neuronal- and glial-like characteristics. Natural agents such as cyclic AMP and butyrate can induce the cells to differentiate along either neuronal or glial cell lines as assessed morphologically and immunocytochemically. Of interest is that combination of agents such as butyrate and laminin, an extracellular attachment protein, yield totally different morphologies, in this case, pigment epithelial in nature. Tissue culture studies thus not only show the primitive, multipotential nature of the Rb cells but their great plasticity as well. Such studies are also useful in elucidating the multiple factors (e.g., substrata and soluble agents) which code for normal retinal development from embryo to adult.