Transforming growth-factor-alpha modulates replication and differentiation markers on a human neuroblastoma cell-line

The effects of TGF alpha and EGF on a human neuroblastoma cell line expressing EGF receptor were studied. Both growth factors were mitogenic for neuroblastoma and, at the same time, induced a morphological differentiation. TGF alpha treatment (10 ng/ml) determined an increase in the expression of laminin and neurofilaments, both markers typical of neuronal phenotype. Hovewer, unlike the differentiation induced by retinoic acid treatment, TGF alpha modulation of neuroblastoma neuronal markers was not mediated by an increase in the expression of the ret oncogene. Moreover, TGF alpha appeared to stimulate an autocrine production of TGF alpha itself, as evaluated by an increase in mRNA at three days of treatment. These data suggest a possible involvement of EGF and TGF alpha in a paracrine and autocrine control of neuroblastoma, possibly each accomplishing similar but complementary functions.