Role of Nerve Growth Factor Receptor in Differentiation, Maturation and Spontaneous Regression of Human Neuroblastoma

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Nerve growth factor (NGF) plays an important role in the cell differentiton, maturation and survival of neural crest cells. The purpose of this study is to characterize the function of NGF,NGF receptor, signal transduction in cell differentiation, maturation and spontaneous regression of human neuroblastoma (NB), and eventually to improve the poor prognosis of patients with advanced NB.The following results were obtained.1) trk A (high affinity receptor of NGF) expressions in NB cell lines :The trk A expressions were observed in 6 of 14 NB cell lines (43%).2) trk A and fos expressions by NGF treatment :Alteration of trk A and fos (early gene) expressions by NGF treatment was determined in 3 NB cell lines, including one trk A negative expressing KP-N-RT cell line, and two trk positive expressing NB-1 and KP-N-SIFA cell lines. The expression of fos was not induced in KP-N-RT,whereas these were induced in NB-1 and KP-N-SIFA.3) trk A and fos expressions by gamma-interferon or retinoid folowing by NGF treatment :The expressions of trk A and fos were augmented by either gamma-interferon or retinoid folowing by NGF treatment, as compared with NGF treatment alone. Phosphorylation of trk A protein was observed by Western blot analysis. These resulsts revealed trk A positive expressing NB cell lines could respond to NGF,and cell signal could be transducted into fos early gene in nucleus. This transdution was augmented by gamma-interferon or retinoid treatment.Thus the analysis of cell signal tranduction by NGF may distinguish cell differentiation, maturation and spontaneous regresion observed in infant NB,or cell proliferation observed in child NB.