TRANSFORMING GROWTH-FACTOR-BETA REGULATES DIFFERENTIATION AND PROLIFERATION OF HUMAN NEUROBLASTOMA

The effects of transforming growth factor-beta 1 (TGF beta) on two hum an neuroblastoma cell lines, LAN-5 and SK-N-AS, and one human glioblas toma cell line, GL15, were evaluated. Of the three cultures, only two, SK-N-AS and GL15, had a complete response to TGF beta, with induction of the following effects: (i) inhibition of cell proliferation; (ii) up-regulation of the extracellular matrix glycoprotein fibronectin, to gether with down-regulation of the VLA5 integrin receptor; (iii) up-re gulation of histotype-specific cytoskeletal intermediate filaments (ne urofilaments for neuroblastoma and GFAP for glioblastoma); and (iv) in crease in the glycoprotein CD44, only in SK-N-AS. In the third cell li ne, neuroblastoma LAN-5, the effects exerted by TGF beta consisted onl y of (i) neurofilament increase and (ii) morphological differentiation . The TGF beta 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 rece ptors. These data suggest that TGF beta can induce a histotype-specifi c cell maturation and that the neuroblastoma expressing low type II an d at the same time lacking type III receptor responds only partially t o TGF beta, with induction of neural differentiation but without inhib ition of cell growth. (C) 1996 Academic Press, Inc.