Transforming growth factor beta regulates differentiation and proliferation of human neuroblastoma.

The effects of transforming growth factor-beta1 (TGFbeta) on two human neuroblastoma cell lines, LAN-5 and SK-N-AS, and one human glioblastoma cell line, GL15, were evaluated. Of the three cultures, only two, SK-N-AS and GL15, had a complete response to TGFbeta, with induction of the following effects: (i) inhibition of cell proliferation; (ii) up-regulation of the extracellular matrix glycoprotein fibronectin, together with down-regulation of the VLA5 integrin receptor; (iii) up-regulation of histotype-specific cytoskeletal intermediate filaments (neurofilaments for neuroblastoma and GFAP for glioblastoma); and (iv) increase in the glycoprotein CD44, only in SK-N-AS. In the third cell line, neuroblastoma LAN-5, the effects exerted by TGFbeta consisted only of (i) neurofilament increase and (ii) morphological differentiation. The TGFbeta receptor pattern was different in each culture: SK-N-AS expressed low rates of type I and type II receptors and high rates of type III receptor; LAN-5 expressed high rates of type I, low rates of type II, and no type III; GL15 expressed high rates of all three receptors. These data suggest that TGFbeta can induce a histotype-specific cell maturation and that the neuroblastoma expressing low type II and at the same time lacking type III receptor responds only partially to TGFbeta, with induction of neural differentiation but without inhibition of cell growth.