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. 1997;75(10):1467–1473. doi: 10.1038/bjc.1997.251

Expression of receptors for gut peptides in human pancreatic adenocarcinoma and tumour-free pancreas.

C Tang 1, I Biemond 1, G J Offerhaus 1, W Verspaget 1, C B Lamers 1
PMCID: PMC2223503  PMID: 9166939

Abstract

Gut hormones that modulate the growth of normal pancreas may also modulate the growth of cancers originating from pancreas. This study visualized and compared the receptors for cholecystokinin (CCK), bombesin (BBS), secretin and vasoactive intestinal peptide (VIP) in tumour-free tissue sections of human pancreas (n = 10) and pancreatic ductal adenocarcinomas (n = 12) with storage phosphor autoradiography using radioligands. CCK-B receptors, present in control pancreata, were not detected in any of the pancreatic cancers. BBS receptors were visualized in control pancreata, but they were absent in 10 of 12 pancreatic cancers. In 5 of 12 pancreatic cancers, receptors for secretin were visualized, while binding for secretin was present in all tumour-free pancreata. Conversely, no specific binding of VIP was detected in control pancreata but was identified in 3 of 12 pancreatic cancer specimens. It is concluded that the expression of gut peptide receptors in pancreatic cancer differs from that in tumour-free pancreas. Receptors for these peptides are present in only a minority of pancreatic cancer specimens.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbruzzese J. L., Gholson C. F., Daugherty K., Larson E., DuBrow R., Berlin R., Levin B. A pilot clinical trial of the cholecystokinin receptor antagonist MK-329 in patients with advanced pancreatic cancer. Pancreas. 1992;7(2):165–171. doi: 10.1097/00006676-199203000-00006. [DOI] [PubMed] [Google Scholar]
  2. Adamou J. E., Aiyar N., Van Horn S., Elshourbagy N. A. Cloning and functional characterization of the human vasoactive intestinal peptide (VIP)-2 receptor. Biochem Biophys Res Commun. 1995 Apr 17;209(2):385–392. doi: 10.1006/bbrc.1995.1515. [DOI] [PubMed] [Google Scholar]
  3. Alexander R. W., Upp J. R., Jr, Poston G. J., Townsend C. M., Jr, Singh P., Thompson J. C. Bombesin inhibits growth of human pancreatic adenocarcinoma in nude mice. Pancreas. 1988;3(3):297–302. doi: 10.1097/00006676-198805000-00010. [DOI] [PubMed] [Google Scholar]
  4. Bell R. H., Jr, Kuhlmann E. T., Jensen R. T., Longnecker D. S. Overexpression of cholecystokinin receptors in azaserine-induced neoplasms of the rat pancreas. Cancer Res. 1992 Jun 15;52(12):3295–3299. [PubMed] [Google Scholar]
  5. Cantor P., Olsen O., Gertz B. J., Gjorup I., Worning H. Inhibition of cholecystokinin-stimulated pancreaticobiliary output in man by the cholecystokinin receptor antagonist MK-329. Scand J Gastroenterol. 1991 Jun;26(6):627–637. doi: 10.3109/00365529109043637. [DOI] [PubMed] [Google Scholar]
  6. Domschke S., Domschke W., Rösch W., Konturek S. J., Sprügel W., Mitznegg P., Wünsch E., Demling L. Vasoactive intestinal peptide: a secretin-like partial agonist for pancreatic secretion in man. Gastroenterology. 1977 Sep;73(3):478–480. [PubMed] [Google Scholar]
  7. Edwards B. F., Redding T. W., Schally A. V. The effect of gastrointestinal hormones on the incorporation of tritiated thymidine in the pancreatic adenocarcinoma cell line (WD PaCa). Int J Pancreatol. 1989 Sep;5(2):191–201. doi: 10.1007/BF02924419. [DOI] [PubMed] [Google Scholar]
  8. Ensinck J. W., Laschansky E. C., Vogel R. E., Simonowitz D. A., Roos B. A., Francis B. H. Circulating prosomatostatin-derived peptides. Differential responses to food ingestion. J Clin Invest. 1989 May;83(5):1580–1589. doi: 10.1172/JCI114055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Estival A., Clemente F., Ribet A. Adenocarcinoma of the human exocrine pancreas: presence of secretin and caerulein receptors. Biochem Biophys Res Commun. 1981 Oct 30;102(4):1336–1341. doi: 10.1016/s0006-291x(81)80158-1. [DOI] [PubMed] [Google Scholar]
  10. Estival A., Mouniélou P., Trocheris V., Scemama J. L., Clemente F., Hollande E., Ribet A. Presence of VIP receptors in a human pancreatic adenocarcinoma cell line. Modulation of the cAMP response during cell proliferation. Biochem Biophys Res Commun. 1983 Mar 29;111(3):958–963. doi: 10.1016/0006-291x(83)91393-1. [DOI] [PubMed] [Google Scholar]
  11. Fahrenkrug J., Pedersen J. H., Yamashita Y., Ottesen B., Hökfelt T., Lundberg J. M. Occurrence of VIP and peptide HM in human pancreas and their influence on pancreatic endocrine secretion in man. Regul Pept. 1987 Jul;18(1):51–61. doi: 10.1016/0167-0115(87)90050-4. [DOI] [PubMed] [Google Scholar]
  12. Fourmy D., Zahidi A., Fabre R., Guidet M., Pradayrol L., Ribet A. Receptors for cholecystokinin and gastrin peptides display specific binding properties and are structurally different in guinea-pig and dog pancreas. Eur J Biochem. 1987 Jun 15;165(3):683–692. doi: 10.1111/j.1432-1033.1987.tb11495.x. [DOI] [PubMed] [Google Scholar]
  13. Jiang S., Ulrich C. Molecular cloning and functional expression of a human pancreatic secretin receptor. Biochem Biophys Res Commun. 1995 Feb 27;207(3):883–890. doi: 10.1006/bbrc.1995.1268. [DOI] [PubMed] [Google Scholar]
  14. Johnson F. E., LaRegina M. C., Martin S. A., Bashiti H. M. Cholecystokinin inhibits pancreatic and hepatic carcinogenesis. Cancer Detect Prev. 1983;6(3):389–402. [PubMed] [Google Scholar]
  15. Kumamoto T., Sumii K., Haruma K., Tari A., Tanaka K., Kajiyama G. Gastrin receptors in the human gastrointestinal tract and pancreas. Gastroenterol Jpn. 1989 Apr;24(2):109–114. doi: 10.1007/BF02774183. [DOI] [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Laburthe M., Couvineau A., Amiranoff B., Voisin T. Receptors for gut regulatory peptides. Baillieres Clin Endocrinol Metab. 1994 Jan;8(1):77–110. doi: 10.1016/s0950-351x(05)80227-7. [DOI] [PubMed] [Google Scholar]
  18. Le Meuth V., Philouze-Rome V., Le Huerou-Luron I., Formal M., Vaysse N., Gespach C., Guilloteau P., Fourmy D. Differential expression of A- and B-subtypes of cholecystokinin/gastrin receptors in the developing calf pancreas. Endocrinology. 1993 Sep;133(3):1182–1191. doi: 10.1210/endo.133.3.8365360. [DOI] [PubMed] [Google Scholar]
  19. Liehr R. M., Melnykovych G., Solomon T. E. Growth effects of regulatory peptides on human pancreatic cancer lines PANC-1 and MIA PaCa-2. Gastroenterology. 1990 Jun;98(6):1666–1674. doi: 10.1016/0016-5085(90)91105-f. [DOI] [PubMed] [Google Scholar]
  20. Longnecker D. S. Hormones and pancreatic cancer. Int J Pancreatol. 1991 Summer;9:81–86. doi: 10.1007/BF02925582. [DOI] [PubMed] [Google Scholar]
  21. Malesci A., De Fazio C., Festorazzi S., Bonato C., Valentini A., Tacconi M., Rovati L., Setnikar I. Effect of loxiglumide on gallbladder contractile response to cerulein and food in humans. Gastroenterology. 1990 May;98(5 Pt 1):1307–1310. doi: 10.1016/0016-5085(90)90349-6. [DOI] [PubMed] [Google Scholar]
  22. Marongiu L., Perra M. T., Pinna A. D., Sirigu F., Sirigu P. Peptidergic (VIP) nerves in normal human pancreas and in pancreatitis: an immunohistochemical study. Histol Histopathol. 1993 Jan;8(1):127–132. [PubMed] [Google Scholar]
  23. Meijers M., Woutersen R. A., van Garderen-Hoetmer A., Bakker G. H., de Jong F. H., Foekens J. A., Klijn J. G. Effects of sandostatin and castration on pancreatic carcinogenesis in rats and hamsters. Int J Cancer. 1992 Jan 21;50(2):246–251. doi: 10.1002/ijc.2910500214. [DOI] [PubMed] [Google Scholar]
  24. Meijers M., van Garderen-Hoetmer A., Lamers C. B., Rovati L. C., Jansen J. B., Woutersen R. A. Effects of bombesin on the development of N-nitrosobis(2-oxopropyl)amine-induced pancreatic lesions in hamsters. Cancer Lett. 1991 Jul 26;59(1):45–50. doi: 10.1016/0304-3835(91)90134-4. [DOI] [PubMed] [Google Scholar]
  25. Meijers M., van Garderen-Hoetmer A., Lamers C. B., Rovati L. C., Jansen J. B., Woutersen R. A. Role of cholecystokinin in the development of BOP-induced pancreatic lesions in hamsters. Carcinogenesis. 1990 Dec;11(12):2223–2226. doi: 10.1093/carcin/11.12.2223. [DOI] [PubMed] [Google Scholar]
  26. Munson P. J., Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem. 1980 Sep 1;107(1):220–239. doi: 10.1016/0003-2697(80)90515-1. [DOI] [PubMed] [Google Scholar]
  27. Nio Y., Tsubono M., Morimoto H., Kawabata K., Masai Y., Hayashi H., Manabe T., Imamura M., Fukumoto M. Loxiglumide (CR1505), a cholecystokinin antagonist, specifically inhibits the growth of human pancreatic cancer lines xenografted into nude mice. Cancer. 1993 Dec 15;72(12):3599–3606. doi: 10.1002/1097-0142(19931215)72:12<3599::aid-cncr2820721209>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  28. Poston G. J., Gillespie J., Guillou P. J. Biology of pancreatic cancer. Gut. 1991 Jul;32(7):800–812. doi: 10.1136/gut.32.7.800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Poston G. J., Yao C. Z., Upp J. R., Jr, Alexander R. W., Townsend C. M., Jr, Thompson J. C. Vasoactive intestinal peptide inhibits the growth of hamster pancreatic cancer but not human pancreatic cancer in vivo. Pancreas. 1988;3(4):439–443. doi: 10.1097/00006676-198808000-00012. [DOI] [PubMed] [Google Scholar]
  30. Qin Y., Ertl T., Cai R. Z., Halmos G., Schally A. V. Inhibitory effect of bombesin receptor antagonist RC-3095 on the growth of human pancreatic cancer cells in vivo and in vitro. Cancer Res. 1994 Feb 15;54(4):1035–1041. [PubMed] [Google Scholar]
  31. Robberecht P., De Neef P., Waelbroeck M., Camus J. C., Scemama J. L., Fourmy D., Pradayrol L., Vaysse N., Christophe J. Secretin receptors in human pancreatic membranes. Pancreas. 1988;3(5):529–535. doi: 10.1097/00006676-198810000-00004. [DOI] [PubMed] [Google Scholar]
  32. Sankaran H., Goldfine I. D., Deveney C. W., Wong K. Y., Williams J. A. Binding of cholecystokinin to high affinity receptors on isolated rat pancreatic acini. J Biol Chem. 1980 Mar 10;255(5):1849–1853. [PubMed] [Google Scholar]
  33. Scemama J. L., Zahidi A., Fourmy D., Fagot-Revurat P., Vaysse N., Pradayrol L., Ribet A. Interaction of [125I]-Tyr4-bombesin with specific receptors on normal human pancreatic membranes. Regul Pept. 1986 Jan;13(2):125–132. doi: 10.1016/0167-0115(86)90220-x. [DOI] [PubMed] [Google Scholar]
  34. Silvente-Poirot S., Dufresne M., Vaysse N., Fourmy D. The peripheral cholecystokinin receptors. Eur J Biochem. 1993 Aug 1;215(3):513–529. doi: 10.1111/j.1432-1033.1993.tb18061.x. [DOI] [PubMed] [Google Scholar]
  35. Singh P., Townsend C. M., Jr, Poston G. J., Reubi J. C. Specific binding of cholecystokinin, estradiol and somatostatin to human pancreatic cancer xenografts. J Steroid Biochem Mol Biol. 1991 Nov;39(5A):759–767. doi: 10.1016/0960-0760(91)90377-h. [DOI] [PubMed] [Google Scholar]
  36. Smith J. P., Kramer S. T., Solomon T. E. CCK stimulates growth of six human pancreatic cancer cell lines in serum-free medium. Regul Pept. 1991 Feb 26;32(3):341–349. doi: 10.1016/0167-0115(91)90027-e. [DOI] [PubMed] [Google Scholar]
  37. Smith J. P., Solomon T. E., Bagheri S., Kramer S. Cholecystokinin stimulates growth of human pancreatic adenocarcinoma SW-1990. Dig Dis Sci. 1990 Nov;35(11):1377–1384. doi: 10.1007/BF01536744. [DOI] [PubMed] [Google Scholar]
  38. Tang C., Biemond I., Appel M. J., Visser C. J., Woutersen R. A., Lamers C. B. Expression of receptors for gut peptides in pancreata of BOP-treated and control hamsters. Carcinogenesis. 1996 Oct;17(10):2171–2175. doi: 10.1093/carcin/17.10.2171. [DOI] [PubMed] [Google Scholar]
  39. Tang C., Biemond I., Lamers C. B. Localization and quantification of cholecystokinin receptors in rat brain with storage phosphor autoradiography. Biotechniques. 1995 May;18(5):886–889. [PubMed] [Google Scholar]
  40. Virgolini I., Raderer M., Kurtaran A., Angelberger P., Banyai S., Yang Q., Li S., Banyai M., Pidlich J., Niederle B. Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors. N Engl J Med. 1994 Oct 27;331(17):1116–1121. doi: 10.1056/NEJM199410273311703. [DOI] [PubMed] [Google Scholar]
  41. Wank S. A., Pisegna J. R., de Weerth A. Cholecystokinin receptor family. Molecular cloning, structure, and functional expression in rat, guinea pig, and human. Ann N Y Acad Sci. 1994 Mar 23;713:49–66. doi: 10.1111/j.1749-6632.1994.tb44052.x. [DOI] [PubMed] [Google Scholar]
  42. Yu D. H., Noguchi M., Zhou Z. C., Villanueva M. L., Gardner J. D., Jensen R. T. Characterization of gastrin receptors on guinea pig pancreatic acini. Am J Physiol. 1987 Dec;253(6 Pt 1):G793–G801. doi: 10.1152/ajpgi.1987.253.6.G793. [DOI] [PubMed] [Google Scholar]
  43. de Muckadell O. B., Fahrenkrug J. Preparation of 125I-labeled synthetic porcine secretin for radioimmunoassay. Scand J Clin Lab Invest. 1976 Nov;36(7):661–668. doi: 10.1080/00365517609054492. [DOI] [PubMed] [Google Scholar]

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