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Cross-Competition between Vasoactive Intestinal Peptide and Somatostatin for Binding to Tumor Cell Membrane Receptors¹

Departments of Nuclear Medicine [I. V., Q. Y., S. L.], Pathology [N. N.], Surgery [B. N.], and Internal Medicine I [W. S., P. V.], University of Vienna, Ludwig Boltzmann Institute for Nuclear Medicine [I. V.], A-1090 Vienna, and Radiochemistry Institute, Research Center Seibersdorf [P. A.], Austria

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 . Binding of ¹²³I-labeled Tyr-3-OCT to A431 cells, in turn, was inhibited by . 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.

¹ This work was supported in part by the Commission for Oncology, University of Vienna, by the Fonds of the Major of the City of Vienna, and by the "Fonds zur Förderung der Wissenschaftlichen Forschung in Österreich."

² To whom requests for reprints should be addressed, at the Department of Nuclear Medicine, University Hospital of Vienna, AKH, Währinger Gürtel 18–20, A-1090 Vienna, Austria. Tel., 0043-1-40400-5550; Fax, 0043-1-40400-5552.

Received 8/10/93. Accepted 10/17/93.

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