Cellular heterogeneity is a common feature of human NB tumors and cell lines. Moreover, the different phe-notypes identified in fresh tumors are similar, if not identical, to those seen in cell lines; thus, cell lines may serve as useful surrogates in the investigation of the biochemical, differentiable, and tumorigenic heterogeneity of human NBs. It is clear that the cell variants differ markedly in growth potential, both in vitro and in vivo. A small amount of experimental data would also suggest that variants differ in the intrinsic sensitivities to commonly used chemotherapeutic agents. It is also clear that "cross-talk" may occur between cell variants within tumors, further influencing tumor viability, tumorigenicity, or response to therapy. The identification of putative stem cells within tumors and characterization in cell culture may offer new opportunities for developing strategies for more effective control of NB.

Acknowledgements. Much of the research and thought represented in this chapter is the result of a highly productive collaboration between myself, J.L. Biedler, and B.A. Spengler. Without their efforts and support, this work would not have been accomplished.

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