The autocrine function of vasoactive intestinal peptide on human neuroblastoma cell growth and differentiation
J. C. Pence and N. A. Shorter
Department of Surgery, Duke University Medical Center, Durham, NC.
Direct associations between serum concentrations and immunohistochemically
detectable vasoactive intestinal peptide (VIP) and maturing neuroblastoma
have been documented. Furthermore, VIP has been shown to induce both the
growth inhibition and morphological differentiation of cultured human
neuroblastoma cell lines. As such, it is hypothesized that VIP may be
operative in the autocrine regulation of neuroblastic growth and
differentiation. To test this hypothesis, VIP-induced differentiation of
human neuroblastoma LA-N-5 cells was performed. Significant concomitant
increases in both intracellular and extracellular VIP concentrations were
observed. In addition, a marked increase in VIP receptor expression was
demonstrated with VIP-induced cellular differentiation. Receptor function
was maintained with enhanced expression, as evidenced by an increase in the
generation of intracellular cyclic adenosine monophosphate in response to
exogenous VIP stimulation. Concomitant enhancement of both intracellular
and extracellular VIP expression, coupled with the induction of functional
specific VIP receptors during VIP-induced differentiation, provides
critical evidence for the autocrine regulation of neuroblastoma maturation
by this peptide.
