Neuroblastoma cell lines are comprised of at least three morphologically distinct phenotypes: neuro-blastic cells (N-type); non-neuronal substrate-adherent cells (S-type), and cells with an intermediate phenotype (I type), with distinct morphologic, biochemical, and tumorigenic properties (see Chap. 8).

I-type cells can be induced to differentiate into N-type or S-type cells under selective culture conditions. Cytotoxic chemotherapeutic regimens can also induce NB maturation (McLaughlin and Urich 1977; Raaf et al. 1982). These observations led to subsequent studies aimed at evaluating induction of differentiation as a therapeutic strategy. A variety of chemicals and biologic response modifiers, including retinoids, histone-deacetylase inhibitors, agents that raise intracellular calcium levels, activators of protein kinase C, neurotrophins, and cytokines, have been shown to suppress tumorigenicity, control growth, and induce NB differentiation of NB cell lines.

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