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British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Jul;85(2):266–272. doi: 10.1054/bjoc.2001.1881

Growing vascular endothelial cells express somatostatin subtype 2 receptors

J C Watson 1, D A Balster 7, B M Gebhardt 2,5, T M O'Dorisio 6, M S O'Dorisio 7, G D Espenan 3, G J Drouant 1, E A Woltering 1,4,5,8
PMCID: PMC2364037  PMID: 11461088

Abstract

We hypothesized that non-proliferating (quiescent) human vascular endothelial cells would not express somatostatin receptor subtype 2 (sst 2) and that this receptor would be expressed when the endothelial cells begin to grow. To test this hypothesis, placental veins were harvested from 6 human placentas and 2 mm vein disks were cultured in 0.3% fibrin gels. Morphometric analysis confirmed that 50–75% of cultured vein disks developed radial capillary growth within 15 days. Sst 2 gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) analysis of the RNA from veins before culture and from tissue-matched vein disks that exhibited an angiogenic response. The sst 2 gene was expressed in the proliferating angiogenic sprouts of human vascular endothelium. The presence of sst 2 receptors on proliferating angiogenic vessels was confirmed by immunohistochemical staining and in vivo scintigraphy. These results suggest that sst 2 may be a unique target for antiangiogenic therapy with sst 2 preferring somatostatin analogues conjugated to radioisotopes or cytotoxic agents. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: somatostatin, somatostatin receptors, receptor subtypes, angiogenesis, vascular endothelium, gene expression

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Selected References

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  1. Albers A. R., O'Dorisio M. S., Balster D. A., Caprara M., Gosh P., Chen F., Hoeger C., Rivier J., Wenger G. D., O'Dorisio T. M. Somatostatin receptor gene expression in neuroblastoma. Regul Pept. 2000 Mar 17;88(1-3):61–73. doi: 10.1016/s0167-0115(99)00121-4. [DOI] [PubMed] [Google Scholar]
  2. Balster D. A., O'Dorisio M. S., Summers M. A., Turman M. A. Segmental expression of somatostatin receptor subtypes sst(1) and sst(2) in tubules and glomeruli of human kidney. Am J Physiol Renal Physiol. 2001 Mar;280(3):F457–F465. doi: 10.1152/ajprenal.2001.280.3.F457. [DOI] [PubMed] [Google Scholar]
  3. Barrie R., Woltering E. A., Hajarizadeh H., Mueller C., Ure T., Fletcher W. S. Inhibition of angiogenesis by somatostatin and somatostatin-like compounds is structurally dependent. J Surg Res. 1993 Oct;55(4):446–450. doi: 10.1006/jsre.1993.1167. [DOI] [PubMed] [Google Scholar]
  4. Bhathena S. J., Louie J., Schechter G. P., Redman R. S., Wahl L., Recant L. Identification of human mononuclear leukocytes bearing receptors for somatostatin and glucagon. Diabetes. 1981 Feb;30(2):127–131. doi: 10.2337/diab.30.2.127. [DOI] [PubMed] [Google Scholar]
  5. Bootsma A. H., van Eijck C., Schouten K. K., Reubi J. C., Waser B., Foekens J. A., van Pel R., Zwarthoff E. C., Lamberts S. W., de Klein A. Somatostatin receptor-positive primary breast tumors: genetic, patient and tumor characteristics. Int J Cancer. 1993 May 28;54(3):357–362. doi: 10.1002/ijc.2910540302. [DOI] [PubMed] [Google Scholar]
  6. Brown K. J., Maynes S. F., Bezos A., Maguire D. J., Ford M. D., Parish C. R. A novel in vitro assay for human angiogenesis. Lab Invest. 1996 Oct;75(4):539–555. [PubMed] [Google Scholar]
  7. Cuntz M. C., Levine E. A., O'Dorisio T. M., Watson J. C., Wray D. A., Espenan G. D., McKnight C., Meier J. R., Weber L. J., Mera R. Intraoperative gamma detection of 125I-lanreotide in women with primary breast cancer. Ann Surg Oncol. 1999 Jun;6(4):367–372. doi: 10.1007/s10434-999-0367-y. [DOI] [PubMed] [Google Scholar]
  8. Denzler B., Reubi J. C. Expression of somatostatin receptors in peritumoral veins of human tumors. Cancer. 1999 Jan 1;85(1):188–198. doi: 10.1002/(sici)1097-0142(19990101)85:1<188::aid-cncr26>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  9. Espenan G. D., Nelson J. A., Fisher D. R., Diaco D. S., McCarthy K. E., Anthony L. B., Maloney T. J., Woltering E. A. Experiences with high dose radiopeptide therapy: the health physics perspective. Health Phys. 1999 Mar;76(3):225–235. doi: 10.1097/00004032-199903000-00001. [DOI] [PubMed] [Google Scholar]
  10. Kälkner K. M., Nilsson S., Westlin J. E. [111In-DTPA-D-Phe1]-octreotide scintigraphy in patients with hormone-refractory prostatic adenocarcinoma can predict therapy outcome with octreotide treatment: a pilot study. Anticancer Res. 1998 Jan-Feb;18(1B):513–516. [PubMed] [Google Scholar]
  11. Martinez D. A., O'Dorisio M. S., O'Dorisio T. M., Qualman S. J., Caniano D. A., Teich S., Besner G. E., King D. R. Intraoperative detection and resection of occult neuroblastoma: a technique exploiting somatostatin receptor expression. J Pediatr Surg. 1995 Nov;30(11):1580–1589. doi: 10.1016/0022-3468(95)90161-2. [DOI] [PubMed] [Google Scholar]
  12. McCarthy K. E., Woltering E. A., Espenan G. D., Cronin M., Maloney T. J., Anthony L. B. In situ radiotherapy with 111In-pentetreotide: initial observations and future directions. Cancer J Sci Am. 1998 Mar-Apr;4(2):94–102. [PubMed] [Google Scholar]
  13. Meyers M. O., Anthony C. T., Coy D. H., Murphy W. A., Drouant G. J., Fuselier J., Espenan G. D., Maloney T. J., Woltering E. A. Multiply radioiodinated somatostatin analogs induce receptor-specific cytotoxicity. J Surg Res. 1998 May;76(2):154–158. doi: 10.1006/jsre.1998.5313. [DOI] [PubMed] [Google Scholar]
  14. Nilsson S., Reubi J. C., Kalkner K. M., Laissue J. A., Horisberger U., Olerud C., Westlin J. E. Metastatic hormone-refractory prostatic adenocarcinoma expresses somatostatin receptors and is visualized in vivo by [111In]-labeled DTPA-D-[Phe1]-octreotide scintigraphy. Cancer Res. 1995 Dec 1;55(23 Suppl):5805s–5810s. [PubMed] [Google Scholar]
  15. O'Dorisio M. S., Chen F., O'Dorisio T. M., Wray D., Qualman S. J. Characterization of somatostatin receptors on human neuroblastoma tumors. Cell Growth Differ. 1994 Jan;5(1):1–8. [PubMed] [Google Scholar]
  16. Patel P. C., Barrie R., Hill N., Landeck S., Kurozawa D., Woltering E. A. Postreceptor signal transduction mechanisms involved in octreotide-induced inhibition of angiogenesis. Surgery. 1994 Dec;116(6):1148–1152. [PubMed] [Google Scholar]
  17. Plonowski A., Schally A. V., Nagy A., Kiaris H., Hebert F., Halmos G. Inhibition of metastatic renal cell carcinomas expressing somatostatin receptors by a targeted cytotoxic analogue of somatostatin AN-238. Cancer Res. 2000 Jun 1;60(11):2996–3001. [PubMed] [Google Scholar]
  18. 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]
  19. Schirmer W. J., O'Dorisio T. M., Schirmer T. P., Mojzisik C. M., Hinkle G. H., Martin E. W. Intraoperative localization of neuroendocrine tumors with 125I-TYR(3)-octreotide and a hand-held gamma-detecting probe. Surgery. 1993 Oct;114(4):745–752. [PubMed] [Google Scholar]
  20. Thompson C. S., O'Dorisio T. M., Woltering E. A. Calcium reverses octreotide inhibition of insulin and glucagon levels in patients with insulinoma and glucagonoma. Digestion. 1996;57 (Suppl 1):62–68. doi: 10.1159/000201399. [DOI] [PubMed] [Google Scholar]
  21. Vanhagen P. M., Markusse H. M., Lamberts S. W., Kwekkeboom D. J., Reubi J. C., Krenning E. P. Somatostatin receptor imaging. The presence of somatostatin receptors in rheumatoid arthritis. Arthritis Rheum. 1994 Oct;37(10):1521–1527. doi: 10.1002/art.1780371017. [DOI] [PubMed] [Google Scholar]
  22. Woltering E. A., Barrie R., O'Dorisio T. M., Arce D., Ure T., Cramer A., Holmes D., Robertson J., Fassler J. Somatostatin analogues inhibit angiogenesis in the chick chorioallantoic membrane. J Surg Res. 1991 Mar;50(3):245–251. doi: 10.1016/0022-4804(91)90186-p. [DOI] [PubMed] [Google Scholar]
  23. Woltering E. A., Barrie R., O'Dorisio T. M., O'Dorisio M. S., Nance R., Cook D. M. Detection of occult gastrinomas with iodine 125-labeled lanreotide and intraoperative gamma detection. Surgery. 1994 Dec;116(6):1139–1147. [PubMed] [Google Scholar]
  24. Woltering E. A., Ellison E. C., O'Dorisio T. M., Sparks J., Howe B., Dyben T. Somatostatin-like peptides alter calcium but not secretin sensitivity of gastrinoma cells. J Surg Res. 1986 Jun;40(6):605–610. doi: 10.1016/0022-4804(86)90104-6. [DOI] [PubMed] [Google Scholar]
  25. Woltering E. A., O'Dorisio M. S., Murphy W. A., Chen F., Drouant G. J., Espenan G. D., Fisher D. R., Sharma C., Diaco D. S., Maloney T. M. Synthesis and characterization of multiply-tyrosinated, multiply-iodinated somatostatin analogs. J Pept Res. 1999 Feb;53(2):201–213. doi: 10.1111/j.1397-002x.1999.00019.x. [DOI] [PubMed] [Google Scholar]
  26. Woltering E. A., Watson J. C., Alperin-Lea R. C., Sharma C., Keenan E., Kurozawa D., Barrie R. Somatostatin analogs: angiogenesis inhibitors with novel mechanisms of action. Invest New Drugs. 1997;15(1):77–86. doi: 10.1023/a:1005774713202. [DOI] [PubMed] [Google Scholar]
  27. Wynick D., Bloom S. R. Clinical review 23: The use of the long-acting somatostatin analog octreotide in the treatment of gut neuroendocrine tumors. J Clin Endocrinol Metab. 1991 Jul;73(1):1–3. doi: 10.1210/jcem-73-1-1. [DOI] [PubMed] [Google Scholar]
  28. Zamora P. O., Marek M. J., Knapp F. F., Jr Preparation of 188Re-RC-160 somatostatin analog: a peptide for local/regional radiotherapy. Appl Radiat Isot. 1997 Mar;48(3):305–309. doi: 10.1016/s0969-8043(96)00226-6. [DOI] [PubMed] [Google Scholar]

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