Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1997;75(3):360–366. doi: 10.1038/bjc.1997.59

Somatostatin receptor subtype mRNA expression in human colorectal cancer and normal colonic mucosae.

S A Laws 1, A C Gough 1, A A Evans 1, M A Bains 1, J N Primrose 1
PMCID: PMC2063369  PMID: 9020480

Abstract

Somatostatin analogues may be useful novel agents in the systemic treatment of advanced colorectal cancer, as somatostatin inhibits proliferation in a wide variety of cell types. Here, we report the expression profiles of somatostatin receptor mRNAs in 32 pairs of malignant and normal colonic epithelia. Receptor subtype 2 (hSSTR2) mRNA was detected throughout nearly 90% of both malignant and normal tissue by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Subtype 5 (hSSTR5) mRNA was detected in 46% and 45% of tumour and mucosal samples respectively, but in 75% (9/12) of early-stage tumours (tubulovillous adenomas, Dukes' A and B) compared with 31% (5/16) of late-stage tumours (Dukes' C and 'D' tumours), 0.05>P>0.025 (chi2 with Yates' correction). There was also reduced expression of hSSTR5 in samples of metastatic tumour (11%, 1/9) compared with all tumour samples (56%, 18/32) 0.025>P>0.01 (chi2 with Yates' correction). Other hSSTRs (1, 3 and 4) were expressed infrequently. Thus, hSSTR2 expression is retained after malignant transformation in colonic epithelium and, although it may potentially be a target for antiproliferative therapy, its ubiquitous expression militates against this. hSSTR5 warrants investigation as a tumour suppressor.

Full text

PDF
360

Images in this article

Selected References

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

  1. Bell G. I., Reisine T. Molecular biology of somatostatin receptors. Trends Neurosci. 1993 Jan;16(1):34–38. doi: 10.1016/0166-2236(93)90050-v. [DOI] [PubMed] [Google Scholar]
  2. Buscail L., Delesque N., Estève J. P., Saint-Laurent N., Prats H., Clerc P., Robberecht P., Bell G. I., Liebow C., Schally A. V. Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2315–2319. doi: 10.1073/pnas.91.6.2315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buscail L., Estève J. P., Saint-Laurent N., Bertrand V., Reisine T., O'Carroll A. M., Bell G. I., Schally A. V., Vaysse N., Susini C. Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1580–1584. doi: 10.1073/pnas.92.5.1580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cascinu S., Del Ferro E., Catalano G. A randomised trial of octreotide vs best supportive care only in advanced gastrointestinal cancer patients refractory to chemotherapy. Br J Cancer. 1995 Jan;71(1):97–101. doi: 10.1038/bjc.1995.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eden P. A., Taylor J. E. Somatostatin receptor subtype gene expression in human and rodent tumors. Life Sci. 1993;53(1):85–90. doi: 10.1016/0024-3205(93)90614-9. [DOI] [PubMed] [Google Scholar]
  6. Klijn J. G., Hoff A. M., Planting A. S., Verweij J., Kok T., Lamberts S. W., Portengen H., Foekens J. A. Treatment of patients with metastatic pancreatic and gastrointestinal tumours with the somatostatin analogue Sandostatin: a phase II study including endocrine effects. Br J Cancer. 1990 Oct;62(4):627–630. doi: 10.1038/bjc.1990.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lamberts S. W., van der Lely A. J., de Herder W. W., Hofland L. J. Octreotide. N Engl J Med. 1996 Jan 25;334(4):246–254. doi: 10.1056/NEJM199601253340408. [DOI] [PubMed] [Google Scholar]
  8. Liebow C., Reilly C., Serrano M., Schally A. V. Somatostatin analogues inhibit growth of pancreatic cancer by stimulating tyrosine phosphatase. Proc Natl Acad Sci U S A. 1989 Mar;86(6):2003–2007. doi: 10.1073/pnas.86.6.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Miller G. V., Farmery S. M., Woodhouse L. F., Primrose J. N. Somatostatin binding in normal and malignant human gastrointestinal mucosa. Br J Cancer. 1992 Aug;66(2):391–395. doi: 10.1038/bjc.1992.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. O'Carroll A. M., Lolait S. J., König M., Mahan L. C. Molecular cloning and expression of a pituitary somatostatin receptor with preferential affinity for somatostatin-28. Mol Pharmacol. 1992 Dec;42(6):939–946. [PubMed] [Google Scholar]
  11. O'Carroll A. M., Raynor K., Lolait S. J., Reisine T. Characterization of cloned human somatostatin receptor SSTR5. Mol Pharmacol. 1994 Aug;46(2):291–298. [PubMed] [Google Scholar]
  12. Pagliacci M. C., Tognellini R., Grignani F., Nicoletti I. Inhibition of human breast cancer cell (MCF-7) growth in vitro by the somatostatin analog SMS 201-995: effects on cell cycle parameters and apoptotic cell death. Endocrinology. 1991 Nov;129(5):2555–2562. doi: 10.1210/endo-129-5-2555. [DOI] [PubMed] [Google Scholar]
  13. Partsch G., Matucci-Cerinic M. Effect of substance P and somatostatin on migration of polymorphonuclear (PMN) cells in vitro. Inflammation. 1992 Oct;16(5):539–547. doi: 10.1007/BF00918978. [DOI] [PubMed] [Google Scholar]
  14. Patel Y. C., Greenwood M. T., Warszynska A., Panetta R., Srikant C. B. All five cloned human somatostatin receptors (hSSTR1-5) are functionally coupled to adenylyl cyclase. Biochem Biophys Res Commun. 1994 Jan 28;198(2):605–612. doi: 10.1006/bbrc.1994.1088. [DOI] [PubMed] [Google Scholar]
  15. Pinski J., Halmos G., Yano T., Szepeshazi K., Qin Y., Ertl T., Schally A. V. Inhibition of growth of MKN45 human gastric-carcinoma xenografts in nude mice by treatment with bombesin/gastrin-releasing-peptide antagonist (RC-3095) and somatostatin analogue RC-160. Int J Cancer. 1994 May 15;57(4):574–580. doi: 10.1002/ijc.2910570422. [DOI] [PubMed] [Google Scholar]
  16. Qin Y., Schally A. V., Willems G. Treatment of liver metastases of human colon cancers in nude mice with somatostatin analogue RC-160. Int J Cancer. 1992 Nov 11;52(5):791–796. doi: 10.1002/ijc.2910520520. [DOI] [PubMed] [Google Scholar]
  17. Radulovic S., Comaru-Schally A. M., Milovanovic S., Schally A. V. Somatostatin analogue RC-160 and LH-RH antagonist SB-75 inhibit growth of MIA PaCa-2 human pancreatic cancer xenografts in nude mice. Pancreas. 1993 Jan;8(1):88–97. doi: 10.1097/00006676-199301000-00016. [DOI] [PubMed] [Google Scholar]
  18. Raynor K., Murphy W. A., Coy D. H., Taylor J. E., Moreau J. P., Yasuda K., Bell G. I., Reisine T. Cloned somatostatin receptors: identification of subtype-selective peptides and demonstration of high affinity binding of linear peptides. Mol Pharmacol. 1993 Jun;43(6):838–844. [PubMed] [Google Scholar]
  19. Reubi J. C., Horisberger U., Laissue J. High density of somatostatin receptors in veins surrounding human cancer tissue: role in tumor-host interaction? Int J Cancer. 1994 Mar 1;56(5):681–688. doi: 10.1002/ijc.2910560513. [DOI] [PubMed] [Google Scholar]
  20. Rohrer L., Raulf F., Bruns C., Buettner R., Hofstaedter F., Schüle R. Cloning and characterization of a fourth human somatostatin receptor. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4196–4200. doi: 10.1073/pnas.90.9.4196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Smith J. P., Doll D., Croitoru R., Thornton C., Perry M. C. Octreotide has no effect on advanced colon cancer. J Clin Gastroenterol. 1994 Apr;18(3):245–247. doi: 10.1097/00004836-199404000-00020. [DOI] [PubMed] [Google Scholar]
  22. Stewart G. J., Lawson J. A., Morris D. L. Octreotide inhibits development of hepatic metastases from a human colonic cancer cell line. Br J Surg. 1994 Sep;81(9):1332–1332. doi: 10.1002/bjs.1800810924. [DOI] [PubMed] [Google Scholar]
  23. Vidal C., Rauly I., Zeggari M., Delesque N., Esteve J. P., Saint-Laurent N., Vaysse N., Susini C. Up-regulation of somatostatin receptors by epidermal growth factor and gastrin in pancreatic cancer cells. Mol Pharmacol. 1994 Jul;46(1):97–104. [PubMed] [Google Scholar]
  24. Warhurst G., Higgs N. B., Grigor M. R., Ross I., Barbezat G. O. Expression of multiple somatostatin receptor genes in human colonic epithelial cells. Biochem Soc Trans. 1995 Feb;23(1):18S–18S. doi: 10.1042/bst023018s. [DOI] [PubMed] [Google Scholar]
  25. Yamada Y., Kagimoto S., Kubota A., Yasuda K., Masuda K., Someya Y., Ihara Y., Li Q., Imura H., Seino S. Cloning, functional expression and pharmacological characterization of a fourth (hSSTR4) and a fifth (hSSTR5) human somatostatin receptor subtype. Biochem Biophys Res Commun. 1993 Sep 15;195(2):844–852. doi: 10.1006/bbrc.1993.2122. [DOI] [PubMed] [Google Scholar]
  26. Yamada Y., Post S. R., Wang K., Tager H. S., Bell G. I., Seino S. Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):251–255. doi: 10.1073/pnas.89.1.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yamada Y., Reisine T., Law S. F., Ihara Y., Kubota A., Kagimoto S., Seino M., Seino Y., Bell G. I., Seino S. Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase. Mol Endocrinol. 1992 Dec;6(12):2136–2142. doi: 10.1210/mend.6.12.1337145. [DOI] [PubMed] [Google Scholar]
  28. van Eijck C. H., Slooter G. D., Hofland L. J., Kort W., Jeekel J., Lamberts S. W., Marquet R. L. Somatostatin receptor-dependent growth inhibition of liver metastases by octreotide. Br J Surg. 1994 Sep;81(9):1333–1337. doi: 10.1002/bjs.1800810925. [DOI] [PubMed] [Google Scholar]

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

RESOURCES