title: Cross-competition between vasoactive intestinal peptide and somatostatin for binding to tumor cell membrane receptors.
abstract: Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide with a wide range of biological activities. Recent data suggest that functional VIP receptors are expressed on various tumor cells. Somatostatin (SST) and its long-acting analogue octreotide (OCT) are potent inhibitors of tumor cell growth and secretion. In the present study, the interactions between VIP and SST/OCT on primary tumors (insulinomas, n = 3; VIPomas, n = 2; intestinal adenocarcinomas, n = 5; neuroblastomas, n = 5; papillary thyroid cancers, n = 7; carcinoids, n = 5; ductal breast cancers, n = 8; small cell lung cancers, n = 3; ACTH-producing hypophyseal adenomas, n = 5; pheochromocytomas, n = 5) as well as on tumor cell lines (A431, HT29, PANC1, COLO320, HMC1, and KU812 cells) were analyzed by use of 123I-labeled VIP and 123I-labeled Tyr-3-OCT. Cross-competition between VIP and SST/OCT for binding to tumor cells was observed. The rank-order of potency for displacement of 123I-labeled VIP binding to intact A431 cells was VIP [concentration causing half-maximal inhibition (IC50) = 2.9 +/- 1.9 (SD) nM] > OCT (IC50 = 9.3 +/- 1.7 nM) = SST > substance P = secretin (IC50 = 1 microM). Binding of 123I-labeled Tyr-3-OCT to A431 cells, in turn, was inhibited by OCT = Tyr-3-OCT (IC50 = 1.5 +/- 0.3 nM) = SST > VIP (IC50 = 4.9 +/- 1.1 nM). This rank-order of potency was also obtained for primary tumors and tumor cell lines. Furthermore, SST and OCT inhibited VIP-induced [3H]thymidine incorporation, cyclic AMP formation, and tyrosine kinase activity with IC50 values < 10 nM. Together, these data provide evidence for functional interactions between SST and VIP on various tumor cells. These interactions may involve peptide cross-competition at cellular binding sites and may have implications for the biology and pathophysiology of respective cells and disease states.
authors.affiliation: Department of Nuclear Medicine, University of Vienna, Ludwig Boltzmann Institute for Nuclear Medicine, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Virgolini
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: Angelberger
authors.forename: N
authors.initials: N
authors.lastname: Neuhold
authors.forename: B
authors.initials: B
authors.lastname: Niederle
authors.forename: W
authors.initials: W
authors.lastname: Scheithauer
authors.forename: P
authors.initials: P
authors.lastname: Valent
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D003429:Cross Reactions; D000242:Cyclic AMP / Q000096:biosynthesis; D004347:Drug Interactions; D006801:Humans; D008024:Ligands; D008407:Mast Cells / Q000378:metabolism / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism* / Q000648:ultrastructure*; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000648:ultrastructure; D009504:Neutrophils / Q000378:metabolism / Q000648:ultrastructure; D010761:Phosphorus Radioisotopes; D017481:Receptors, Somatostatin / Q000378:metabolism* / Q000502:physiology; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism* / Q000502:physiology; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D008024:Ligands; D010761:Phosphorus Radioisotopes; D017481:Receptors, Somatostatin; D018005:Receptors, Vasoactive Intestinal Peptide; D014316:Tritium; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D013936:Thymidine