Sympathetic Neurotransmitters in Neuroblastoma – Between Physiology and Pathology

Neuroblastomas arise from precursors of sympathetic neurons due to defects in their normal development (Edsjo et al., 2007). Consequently, the tumors exhibit various degrees of neuronal differentiation manifested by expression of markers characteristic for sympathetic neurons and release of their physiological neurotransmitters (Bourdeaut et al., 2009). Since the levels of neuroblastoma cell differentiation determines clinical phenotype of the disease and its outcome, the factors regulating this process have been extensively studied and recently introduced to the clinic (Edsjo et al., 2007; Maris, 2010). Surprisingly, however, little attention has been paid to the role the sympathetic neurotransmitters excessively released from neuroblastoma cells play in this pathological condition. Despite their known role in the regulation of proliferation and survival of other cell types, in the neuroblastoma field those factors have been treated merely as markers of neuronal differentiation. Very often, even if studies on functional effects of neurotransmitters on neuroblastoma cells have been performed, these cells have been considered purely as a neuronal model (Laifenfeld et al., 2002; Lopes et al., 2010). Therefore, the results of such studies have been interpreted in the context of other neurological disorders, but not assessed in terms of their implications for neuroblastoma biology and therapy. Research conducted in our laboratory focuses on growth-promoting functions of one of such neurotransmitters, neuropeptide Y (NPY). We were able to show that this physiological peptide acts as a crucial mitogenic and angiogenic factor for neuroblastomas and significantly contributes to their progression (Kitlinska et al., 2005; Lu et al., 2010). However, the role of other sympathetic neurotransmitters in biology of these tumors remains understudied. This chapter summarizes our current knowledge on the role these molecules play in the regulation of neuroblastoma growth, and identifies problems which thus far have not been addressed.