DIFFERENTIAL EXPRESSION OF PLEIOTROPHIN AND MIDKINE IN ADVANCED NEUROBLASTOMAS

Pleiotrophin (PTN) and midkine (MK) are members of a new family of neu rotrophic factors whose expression is developmentally regulated. PTN a lso transforms NIH 3T3 cells, and MK is mitogenic to certain cell line s. Neuroblastomas are tumors derived from neural crest cells, and rece nt studies have revealed that the biology of these tumors is at least partly regulated by neurotrophic factors and their receptors. To exami ne the expression of PTN and MK in neuroblastoma, we analyzed their mR NA expression in 72 primary neuroblastomas and 11 neuroblastoma cell l ines as well as other tissues and cell lines. PTN is highly expressed in favorable neuroblastomas (stages I, II, and IV-S, n = 44), whereas it is expressed at a significantly lower level in advanced tumors (sta ges III and IV, n = 28, P = 0.003). PTN is not expressed in either agg ressive neuroblastomas with N-myc amplification or in neuroblastoma ce ll lines. Moreover, the expression pattern of PTN was similar to that of TRK-A, the high affinity receptor for nerve growth factor, in that it is correlated with a favorable prognosis (P < 0.004). In contrast, MK is highly expressed in almost all primary neuroblastomas and cell l ines and showed no correlation with disease stage or N-myc amplificati on. These results suggest that differential expression of PTN and MK m ay have an important role in regulating growth and differentiation of neuroblastomas.