The
insulin-like growth factors (IGFs) are known to stimulate both the proliferation and differentiation of
neuroblastoma cells, but the role of the
IGF binding proteins (IGFBPs) has not yet been established. In this study, human
neuroblastoma SH-SY5Y cells have been treated with
IGF-I and its potent analogue
des(1-3)IGF-I alone or following preincubation with a differentiating agent such as 12-o-tetradecanoylphorbol-13-acetate (TPA). Cell proliferation and differentiation were evaluated.
Conditioned medium was tested for the presence of IGFBPs by
ligand blotting. The SH-SY5Y cell proliferation was maximally stimulated by
des(1-3)IGF-I. The TPA-induced differentiation of SH-SY5Y, evaluated by assessment of cell morphology and
GAP-43 expression as a
biochemical marker of differentiation was potentiated by nanomolar concentrations of
des(1-3)IGF-I and, to a smaller extent,
IGF-I Conditioned medium showed the presence of a major
IGFBP band with an approximate molecular weight of 32.5 kD and a very faint band of approximately 24kD. The
IGFBP immunoblotting results suggest that the predominant band might represent
IGFBP-2. Our data represent a first demonstration of the presence of IGFBPs in
conditioned medium of human
neuroblastoma SH-SY5Y cells. The finding that the potent
IGF-I analogue
des(1-3)IGF-I with reduced affinity for IGFBPs induce major effects on cell growth and differentiation suggests that the IGFBPs may play an active role in the neuronal response to the proliferative and differentiative effects of
IGF-I.