Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1998 Feb;77(4):632–637. doi: 10.1038/bjc.1998.101

Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours.

O Nilsson 1, L Kölby 1, B Wängberg 1, A Wigander 1, H Billig 1, L William-Olsson 1, M Fjälling 1, E Forssell-Aronsson 1, H Ahlman 1
PMCID: PMC2149934  PMID: 9484822

Abstract

We have compared the expression of somatostatin receptor (sstr) subtypes with the outcome of somatostatin receptor scintigraphy and the effect of somatostatin receptor activation in patients with disseminated carcinoid tumours. Tumour tissues from nine patients with midgut carcinoids (ileal) and three patients with foregut carcinoids (gastric, thymic) were analysed using Northern blotting. Expression of somatostatin receptors was demonstrated in all tumours (12 out of 12), with all five receptor subtypes present in 9 out of 12 tumours. Somatostatin receptor scintigraphy using [111In]DTPA-D-Phe1-octreotide visualized tumours in all patients (12 out of 12). The 111In activity concentrations in tumour tissue (T) and blood (B) were determined in three tumours 1-7 days after injection of the radionuclide. The T/B 111In activity concentration ratios ranged between 32 and 651. Clinically, treatment with the long-acting somatostatin analogue octreotide resulted in marked symptom relief accompanied by a significant reduction in tumour markers, for example urinary-5-HIAA levels (28-71% reduction). Incubation of midgut carcinoid tumours in primary culture with octreotide (10 microM) resulted in a reduction in spontaneously secreted serotonin (45-71% reduction) and 5-HIAA (41-94% reduction). The results demonstrate that carcinoid tumours possess multiple somatostatin receptor subtypes and that somatostatin analogues such as octreotide, which preferentially bind to somatostatin receptor subtype 2 and 5, can be used in the diagnosis and medical treatment of these tumours. In the future, novel somatostatin analogues with subtype specific receptor profiles may prove to be of value for individualizing the treatment of disseminated carcinoid tumour disease.

Full text

PDF
632

Images in this article

635Figure 1
on p.635

Selected References

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

  1. Ahlman H., Wängberg B., Tisell L. E., Nilsson O., Fjälling M., Forssell-Aronsson E. Clinical efficacy of octreotide scintigraphy in patients with midgut carcinoid tumours and evaluation of intraoperative scintillation detection. Br J Surg. 1994 Aug;81(8):1144–1149. doi: 10.1002/bjs.1800810820. [DOI] [PubMed] [Google Scholar]
  2. Andersson P., Forssell-Aronsson E., Johanson V., Wängberg B., Nilsson O., Fjälling M., Ahlman H. Internalization of indium-111 into human neuroendocrine tumor cells after incubation with indium-111-DTPA-D-Phe1-octreotide. J Nucl Med. 1996 Dec;37(12):2002–2006. [PubMed] [Google Scholar]
  3. Arnold R., Trautmann M. E., Creutzfeldt W., Benning R., Benning M., Neuhaus C., Jürgensen R., Stein K., Schäfer H., Bruns C. Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours. Gut. 1996 Mar;38(3):430–438. doi: 10.1136/gut.38.3.430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bakker W. H., Krenning E. P., Reubi J. C., Breeman W. A., Setyono-Han B., de Jong M., Kooij P. P., Bruns C., van Hagen P. M., Marbach P. In vivo application of [111In-DTPA-D-Phe1]-octreotide for detection of somatostatin receptor-positive tumors in rats. Life Sci. 1991;49(22):1593–1601. doi: 10.1016/0024-3205(91)90053-e. [DOI] [PubMed] [Google Scholar]
  5. Bruns C., Weckbecker G., Raulf F., Kaupmann K., Schoeffter P., Hoyer D., Lübbert H. Molecular pharmacology of somatostatin-receptor subtypes. Ann N Y Acad Sci. 1994 Sep 15;733:138–146. doi: 10.1111/j.1749-6632.1994.tb17263.x. [DOI] [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Evers B. M., Townsend C. M., Jr, Upp J. R., Allen E., Hurlbut S. C., Kim S. W., Rajaraman S., Singh P., Reubi J. C., Thompson J. C. Establishment and characterization of a human carcinoid in nude mice and effect of various agents on tumor growth. Gastroenterology. 1991 Aug;101(2):303–311. doi: 10.1016/0016-5085(91)90004-5. [DOI] [PubMed] [Google Scholar]
  8. Fjälling M., Andersson P., Forssell-Aronsson E., Grétarsdóttir J., Johansson V., Tisell L. E., Wängberg B., Nilsson O., Berg G., Michanek A. Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome. J Nucl Med. 1996 Sep;37(9):1519–1521. [PubMed] [Google Scholar]
  9. Forssell-Aronsson E., Fjälling M., Nilsson O., Tisell L. E., Wängberg B., Ahlman H. Indium-111 activity concentration in tissue samples after intravenous injection of indium-111-DTPA-D-Phe-1-octreotide. J Nucl Med. 1995 Jan;36(1):7–12. [PubMed] [Google Scholar]
  10. Gorden P., Comi R. J., Maton P. N., Go V. L. NIH conference. Somatostatin and somatostatin analogue (SMS 201-995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Intern Med. 1989 Jan 1;110(1):35–50. doi: 10.7326/0003-4819-110-1-35. [DOI] [PubMed] [Google Scholar]
  11. John M., Meyerhof W., Richter D., Waser B., Schaer J. C., Scherübl H., Boese-Landgraf J., Neuhaus P., Ziske C., Mölling K. Positive somatostatin receptor scintigraphy correlates with the presence of somatostatin receptor subtype 2. Gut. 1996 Jan;38(1):33–39. doi: 10.1136/gut.38.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Krenning E. P., Kooij P. P., Pauwels S., Breeman W. A., Postema P. T., De Herder W. W., Valkema R., Kwekkeboom D. J. Somatostatin receptor: scintigraphy and radionuclide therapy. Digestion. 1996;57 (Suppl 1):57–61. doi: 10.1159/000201398. [DOI] [PubMed] [Google Scholar]
  13. Kubota A., Yamada Y., Kagimoto S., Shimatsu A., Imamura M., Tsuda K., Imura H., Seino S., Seino Y. Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors. J Clin Invest. 1994 Mar;93(3):1321–1325. doi: 10.1172/JCI117090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kvols L. K., Moertel C. G., O'Connell M. J., Schutt A. J., Rubin J., Hahn R. G. Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue. N Engl J Med. 1986 Sep 11;315(11):663–666. doi: 10.1056/NEJM198609113151102. [DOI] [PubMed] [Google Scholar]
  15. Nilsson O., Wängberg B., Theodorsson E., Skottner A., Ahlman H. Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth? Int J Cancer. 1992 May 8;51(2):195–203. doi: 10.1002/ijc.2910510206. [DOI] [PubMed] [Google Scholar]
  16. Patel Y. C., Srikant C. B. Subtype selectivity of peptide analogs for all five cloned human somatostatin receptors (hsstr 1-5). Endocrinology. 1994 Dec;135(6):2814–2817. doi: 10.1210/endo.135.6.7988476. [DOI] [PubMed] [Google Scholar]
  17. Raulf F., Pérez J., Hoyer D., Bruns C. Differential expression of five somatostatin receptor subtypes, SSTR1-5, in the CNS and peripheral tissue. Digestion. 1994;55 (Suppl 3):46–53. doi: 10.1159/000201201. [DOI] [PubMed] [Google Scholar]
  18. Reubi J. C., Häcki W. H., Lamberts S. W. Hormone-producing gastrointestinal tumors contain a high density of somatostatin receptors. J Clin Endocrinol Metab. 1987 Dec;65(6):1127–1134. doi: 10.1210/jcem-65-6-1127. [DOI] [PubMed] [Google Scholar]
  19. Reubi J. C., Krenning E., Lamberts S. W., Kvols L. Somatostatin receptors in malignant tissues. J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):1073–1077. doi: 10.1016/0960-0760(90)90468-z. [DOI] [PubMed] [Google Scholar]
  20. Saltz L., Trochanowski B., Buckley M., Heffernan B., Niedzwiecki D., Tao Y., Kelsen D. Octreotide as an antineoplastic agent in the treatment of functional and nonfunctional neuroendocrine tumors. Cancer. 1993 Jul 1;72(1):244–248. doi: 10.1002/1097-0142(19930701)72:1<244::aid-cncr2820720143>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  21. Tisell L. E., Ahlman H., Wängberg B., Hansson G., Mölne J., Nilsson O., Lindstedt G., Fjälling M., Forssell-Aronsson E. Somatostatin receptor scintigraphy in medullary thyroid carcinoma. Br J Surg. 1997 Apr;84(4):543–547. [PubMed] [Google Scholar]
  22. Wangberg B., Forssell-Aronsson E., Tisell L. E., Nilsson O., Fjalling M., Ahlman H. Intraoperative detection of somatostatin-receptor-positive neuroendocrine tumours using indium-111-labelled DTPA-D-Phe1-octreotide. Br J Cancer. 1996 Mar;73(6):770–775. doi: 10.1038/bjc.1996.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Westberg G., Ahlman H., Nilsson O., Illerskog A., Wängberg B. Secretory patterns of tryptophan metabolites in midgut carcinoid tumor cells. Neurochem Res. 1997 Aug;22(8):977–983. doi: 10.1023/a:1022422809202. [DOI] [PubMed] [Google Scholar]
  24. Wängberg B., Nilsson O., Theodorsson E., Dahlström A., Ahlman H. The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells. Br J Cancer. 1991 Jul;64(1):23–28. doi: 10.1038/bjc.1991.233. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES