Abstract
Background: Somatostatin is a widely distributed polypeptide that modulates endocrine and exocrine secretion, cell proliferation, and apoptosis by 5 somatostatin receptors (SSTR1–5). The inhibitory effects of somatostatin on tumor growth may be the result of its suppressing the synthesis and/or secretion of growth factors and growth-promoting hormones. Aim: Very little information is available on the effect of somatostatin analogs on adrenal tumors, so we examined SSTR expression in adrenocortical tumors and studied the effect of a somatostatin analog (SOM230) on hormone secretion and cell viability in adrenal cells. Material/subjects and methods: SSTR expression was analyzed by real-time PCR in 13 adrenocortical carcinomas (ACC), 24 aldosterone-producing adenomas (APA), 11 cortisol-producing adenomas (CPA), and 7 normal adrenals (NA), and verified by immunohistochemistry (IHC) in 14 samples. The effect of SOM230 on cortisol or aldosterone secretion in H295R and primary cell cultures was determined by radioimmunoassay, and its effect on viability in H295R and SW13 using the MTT test. Results: SSTR1 and SSTR2 mRNA was expressed in 100% of adrenal tumors. Compared to NA, ACC revealed an increase in almost all SSTR, while only some APA over-expressed SSTR3 and SSTR1. CPA expressed SSTR similar to NA. IHC confirmed the mRNA expression data. At nanomolar concentrations, SOM230 inhibited hormone secretion in primary adrenal cultures and H295R cells, but had no evident effect on cell viability. Conclusions: The evidence of SSTR over-expression (particularly in ACC) and of hormone secretion being inhibited by SOM230 suggests a potential therapeutic role for this broad-spectrum somatostatin analog in adrenal tumors.
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Allolio B, Hahner S, Weismann D, Fassnacht M. Management of adrenocortical carcinoma. Clin Endocrinol 2004, 60: 273–87.
Reincke M. Mutations in adrenocortical tumors. Horm Metab Res 1998, 30: 447–55.
Kirschner LS. Signaling pathways in adrenocortical cancer. Ann N Y Acad Sci 2002, 968: 222–39.
Terzolo M, Pia A, Berruti A, et al. Low-dose monitored mitotane treatment achieves the therapeutic range with manageable side effects in patients with adrenocortical cancer. J Clin Endocrinol Metab 2000, 85: 2234–8.
Terzolo M, Angeli A, Fassnacht M, et al. Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med 2007, 356: 2372–80.
Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol 1999, 20: 157–98.
Susini C, Buscail L. Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol 2006, 17: 1733–42.
Grozinsky-Glasberg S, Grossman AB, Korbonits M. The role of somatostatin analogues in the treatment of neuroendocrine tumours. Mol Cell Endocrinol 2008, 286: 238–50.
Pandha HS, Harrington K, Saini S, Lynn J, Peters M, Waxman J. Secretory symptoms from metastatic adrenal cortical carcinoma responding to octreotide. Postgrad Med J 1995, 71: 229–30.
Chan NN, Isaacs AJ. Lack of response to octreotide in Cushing’s syndrome due to metastatic adrenocortical carcinoma. Postgrad Med J 1999, 75: 96–7.
Florio T, Thellung S, Arena S. Somatostatin and its analog lanreotide inhibit the proliferation of dispersed human non-functioning pituitary adenoma cells in vitro. Eur J Endocrinol 1999, 141: 396–408.
Cheung NW, Boyages SC. Somatostatin-14 and its analog octreotide exert a cytostatic effect on GH3 rat pituitary tumor cell proliferation via a transient G0/G1 cell cycle block. Endocrinology 1995, 136: 4174–81.
Bevan JS. The antitumoral effects of somatostatin analog therapy in acromegaly. J Clin Endocrinol Metab 2005, 90: 1856–63.
Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 2002, 146: 707–16.
Murray RD, Kim K, Ren SG, et al. The novel somatostatin ligand (SOM230) regulates human and rat anterior pituitary hormone secretion. J Clin Endocrinol Metab 2004, 89: 3027–32.
Hofland LJ, van der Hoek J, Feelders R, et al. The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5. Eur J Endocrinol 2005, 152: 645–54.
Pasquali D, Rossi V, Conzo G, et al. Effects of somatostatin analog SOM230 on cell proliferation, apoptosis, and catecholamine levels in cultured pheochromocytoma cells. J Mol Endocrinol 2008, 40: 263–71.
Bruno JF, Xu Y, Song J, Berelowitz M. Tissue distribution of somatostatin receptor subtype messenger ribonucleic acid in the rat. Endocrinology 1993, 133: 2561–7.
Ueberberg B, Tourne H, Redman A, et al. Differential expression of the human somatostatin receptor subtypes sst1 to sst5 in various adrenal tumors and normal adrenal gland. Horm Metab Res 2005, 37: 722–8.
Unger N, Serdink L, Sheu SY, et al. Immunohistochemical determination of somatostatin receptor subtypes 1, 2A, 3, 4 and 5 in various adrenal tumors. Endocr Res 2004, 30: 931–4.
Unger N, Serdiuk I, Sheu SY, et al. Immunohistochemical localization of somatostatin receptor subtypes in benign and malignant adrenal tumors. Clin Endocrinol (Oxf) 2008, 68: 850–7.
Pisarek H, Stepien T, Kubiak R, Pawlikowski M. Somatostatin receptors in human adrenal gland tumors-immunohistochemical study. Folia Histochem Cytobiol 2008, 46: 345–51.
Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 1989, 13: 202–6.
MacFarlane DA. Cancer of the adrenal cortex: the natural history, prognosis and treatment in the study of fifty-five cases. Ann R Coll Surg Engl 1958, 23: 155–86.
Sullivan M, Boileau M, Hodges CV. Adrenal cortical carcinoma. J Urol 1978, 120: 660–5.
Pagès P, Benali N, Saint-Laurent N, et al. Sst2 somatostatin receptor mediates cell cycle arrest and induction of p27(Kip1). Evidence for the role of SHP-1. J Biol Chem 1999, 274: 15186–93.
Sharma K, Patel YC, Srikant CB. Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol Endocrinol 1996, 10: 1688–96.
Florio T. Molecular mechanisms of the antiproliferative activity of somatostatin receptors (SSTRs) in neuroendocrine tumors. Front Biosci 2008, 13: 822–40.
Florio T, Morini M, Villa V, et al. Somatostatin inhibits tumor angiogenesis and growth via somatostatin receptor-3-mediated regulation of endothelial nitric oxide synthase and mitogen-activated protein kinase activities. Endocrinology 2003, 144: 1574–84.
Hofland LJ. Somatostatin and somatostatin receptors in Cushing’s disease. Mol Cell Endocrinol 2008, 286: 199–205.
McDermott JH, Thabit H, Hickey N, et al. ACTH-secreting bronchial carcinoid: a diagnostic and therapeutic challenge. Ir J Med Sci 2008, 177: 269–72.
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Mariniello, B., Finco, I., Sartorato, P. et al. Somatostatin receptor expression in adrenocortical tumors and effect of a new somatostatin analog SOM230 on hormone secretion in vitro and in ex vivo adrenal cells. J Endocrinol Invest 34, e131–e138 (2011). https://doi.org/10.1007/BF03346721
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DOI: https://doi.org/10.1007/BF03346721