PITUITARY ADENYLATE-CYCLASE ACTIVATING PEPTIDE AND ITS RECEPTORS ARE EXPRESSED IN HUMAN NEUROBLASTOMAS

Vasoactive intestinal peptide (VIP) has been considered as an autocrin e growth factor in neuroblastomas. Pituitary adenylate cyclase activat ing polypeptides (PACAPs) are newly recognized members of the VIP fami ly of neurohormones. As compared to VIP, PACAP has been reported to be biologically more potent and more efficient in tissues expressing sel ective PACAP receptors rather than common VIP/PACAP receptors. PACAPs and VIP interact with the same affinity and stimulate adenylate cyclas e activity with the same efficacy and potency on the VIP receptors, bu t PACAPs act also on a more selective PACAP receptor that also recogni zes VIP but with a 100- to 1,000-fold lower affinity. Thus, depending on the type of receptors expressed at a cell surface, PACAP may be mor e potent and efficient than VIP. The capacity of 22 surgical specimens of neuroblastomas and of 5 established cell lines to synthesize PACAP and VIP and to synthesize and express PACAP receptors and VIP recepto rs was studied. Using the reverse transcriptase-polymerase chain (RT-P CR) method with specific primers, we detected the mRNAs coding for PAC AP and VIP in 19 and 3 out of 22 samples, respectively. PACAP mRNA was expressed in 3 of the 5 cell lines studied and VIP mRNA in 4. Using t he same techniques, PACAP and VIP receptors mRNA were detected in 21, and 13 of the 22 tumor samples and in 5 and 1 of the cell lines studie d, respectively. The expression of the PACAP receptor was demonstrated by direct binding studies and/or by the relative potency of PACAPs an d VIP to stimulate adenylate cyclase activity in 16 of the 22 tumors a nd in all the cell lines. In addition, there was no correlation betwee n tumor stage and the expression of mRNA coding for the peptides and t he receptors. The present results demonstrated that PACAP could also b e a candidate as an autocrine regulator of neuroblastoma which a highe r activity than VIP. (C) 1996 Wiley-Liss, Inc.