282
Views
24
CrossRef citations to date
0
Altmetric
Reviews

Somatostatin and somatostatin receptors: implications for neoplastic growth and cancer biology

, MD, , MD & , MD PhD
Pages 1297-1316 | Published online: 14 Aug 2009

Bibliography

  • Brazeau P, Vale W, Burgus R, et al. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 1973;179(68):77-9
  • Pelletier G, Dube D, Puviani R. Somatostatin: electron microscope immunohistochemical localization in secretory neurons of rat hypothalamus. Science 1977;196(4297):1469-70
  • Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol 1999;20(3):157-98
  • Shen LP, Pictet RL, Rutter WJ. Human somatostatin I: sequence of the cDNA. Proc Natl Acad Sci USA 1982;79(15):4575-9
  • Moller LN, Stidsen CE, Hartmann B, Holst JJ. Somatostatin receptors. Biochim Biophys Acta 2003;1616(1):1-84
  • Bruno JF, Xu Y, Song J, Berelowitz M. Molecular cloning and functional expression of a brain-specific somatostatin receptor. Proc Natl Acad Sci USA 1992;89(23):11151-5
  • Meyerhof W, Wulfsen I, Schonrock C, et al. Molecular cloning of a somatostatin-28 receptor and comparison of its expression pattern with that of a somatostatin-14 receptor in rat brain. Proc Natl Acad Sci USA 1992;89(21):10267-71
  • O'Carroll AM, Lolait SJ, Konig M, Mahan LC. Molecular cloning and expression of a pituitary somatostatin receptor with preferential affinity for somatostatin-28. Mol Pharmacol 1992;42(6):939-46
  • Yamada Y, Reisine T, Law SF, et al. Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase. Mol Endocrinol 1992;6(12):2136-42
  • Yamada Y, Post SR, Wang K, et al. Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney. Proc Natl Acad Sci USA 1992;89(1):251-5
  • Rohrer L, Raulf F, Bruns C, et al. Cloning and characterization of a fourth human somatostatin receptor. Proc Natl Acad Sci USA 1993;90(9):4196-200
  • Panetta R, Patel YC. Expression of mRNA for all five human somatostatin receptors (hSSTR1-5) in pituitary tumors. Life Sci 1995;56(5):333-42
  • Hoyer D, Bell GI, Berelowitz M, et al. Classification and nomenclature of somatostatin receptors. Trends Pharmacol Sci 1995;16(3):86-8
  • Patel YC, Srikant CB. Subtype selectivity of peptide analogs for all five cloned human somatostatin receptors (hsstr 1-5). Endocrinology 1994;135(6):2814-7
  • Cescato R, Erchegyi J, Waser B, et al. Design and in vitro characterization of highly sst2-selective somatostatin antagonists suitable for radiotargeting. J Med Chem 2008;51(13):4030-7
  • Wilkinson GF, Feniuk W, Humphrey PP. Characterization of human recombinant somatostatin sst5 receptors mediating activation of phosphoinositide metabolism. Br J Pharmacol 1997;121(1):91-6
  • Schulz S, Handel M, Schreff M, et al. Localization of five somatostatin receptors in the rat central nervous system using subtype-specific antibodies. J Physiol Paris 2000;94(3-4):259-64
  • Kulaksiz H, Eissele R, Rossler D, et al. Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype specific antibodies. Gut 2002;50(1):52-60
  • Zheng H, Bailey A, Jiang MH, et al. Somatostatin receptor subtype 2 knockout mice are refractory to growth hormone-negative feedback on arcuate neurons. Mol Endocrinol 1997;11(11):1709-17
  • Martinez V, Curi AP, Torkian B, et al. High basal gastric acid secretion in somatostatin receptor subtype 2 knockout mice. Gastroenterology 1998;114(6):1125-32
  • Kreienkamp HJ, Akgun E, Baumeister H, et al. Somatostatin receptor subtype 1 modulates basal inhibition of growth hormone release in somatotrophs. FEBS Lett 1999;462(3):464-6
  • Strowski MZ, Kohler M, Chen HY, et al. Somatostatin receptor subtype 5 regulates insulin secretion and glucose homeostasis. Mol Endocrinol 2003;17(1):93-106
  • Rocheville M, Lange DC, Kumar U, et al. Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science 2000;288(5463):154-7
  • Rocheville M, Lange DC, Kumar U, et al. Subtypes of the somatostatin receptor assemble as functional homo- and heterodimers. J Biol Chem 2000;275(11):7862-9
  • Pfeiffer M, Koch T, Schroder H, et al. Heterodimerization of somatostatin and opioid receptors cross-modulates phosphorylation, internalization, and desensitization. J Biol Chem 2002;277(22):19762-72
  • Watt HL, Kharmate GD, Kumar U. Somatostatin receptors 1 and 5 heterodimerize with epidermal growth factor receptor: agonist-dependent modulation of the downstream MAPK signalling pathway in breast cancer cells. Cell Signal 2009;21(3):428-39
  • Guillemin R. Peptides in the brain: the new endocrinology of the neuron. Science 1978;202(4366):390-402
  • Grimberg A. Somatostatin and cancer: applying endocrinology to oncology. Cancer Biol Ther 2004;3(8):731-3
  • Jenkins SA, Kynaston HG, Davies ND, et al. Somatostatin analogs in oncology: a look to the future. Chemotherapy 2001;47(Suppl 2):162-96
  • Weckbecker G, Lewis I, Albert R, et al. Opportunities in somatostatin research: biological, chemical and therapeutic aspects. Nat Rev Drug Discov 2003;2(12):999-1017
  • Reubi JC, Laissue J, Krenning E, Lamberts SW. Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications. J Steroid Biochem Mol Biol 1992;43(1-3):27-35
  • Foekens JA, Portengen H, van Putten WL, et al. Prognostic value of receptors for insulin-like growth factor 1, somatostatin, and epidermal growth factor in human breast cancer. Cancer Res 1989;49 (24 Pt 1):7002-9
  • Corleto VD, Falconi M, Panzuto F, et al. Somatostatin receptor subtypes 2 and 5 are associated with better survival in well-differentiated endocrine carcinomas. Neuroendocrinology 2009;89(2):223-30
  • Ioannou M, Papagelopoulos PJ, Papanastassiou I, et al. Detection of somatostatin receptors in human osteosarcoma. World J Surg Oncol 2008;6:99
  • Jaquet P, Ouafik L, Saveanu A, et al. Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas. J Clin Endocrinol Metab 1999;84(9):3268-76
  • Chanson P. Emerging drugs for acromegaly. Expert Opin Emerg Drugs 2008;13(2):273-93
  • Jaquet P, Saveanu A, Gunz G, et al. Human somatostatin receptor subtypes in acromegaly: distinct patterns of messenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypes. J Clin Endocrinol Metab 2000;85(2):781-92
  • Janson ET, Stridsberg M, Gobl A, et al. Determination of somatostatin receptor subtype 2 in carcinoid tumors by immunohistochemical investigation with somatostatin receptor subtype 2 antibodies. Cancer Res 1998;58(11):2375-8
  • Reubi JC, Kappeler A, Waser B, et al. Immunohistochemical localization of somatostatin receptors sst2A in human tumors. Am J Pathol 1998;153(1):233-45
  • Barakat MT, Meeran K, Bloom SR. Neuroendocrine tumours. Endocr Relat Cancer 2004;11(1):1-18
  • Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;97(4):934-59
  • de Herder WW, Hofland LJ, van der Lely AJ, Lamberts SW. Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours. Endocr Relat Cancer 2003;10(4):451-8
  • Reubi JC, Kvols LK, Waser B, et al. Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. Cancer Res 1990;50(18):5969-77
  • Grozinsky-Glasberg S, Shimon I, Korbonits M, Grossman AB. Somatostatin analogues in the control of neuroendocrine tumours: efficacy and mechanisms. Endocr Relat Cancer 2008;15(3):701-20
  • Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 2003;24(4):389-427
  • Modlin IM, Kidd M, Latich I, et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005;128(6):1717-51
  • Schaer JC, Waser B, Mengod G, Reubi JC. Somatostatin receptor subtypes sst1, sst2, sst3 and sst5 expression in human pituitary, gastroentero-pancreatic and mammary tumors: comparison of mRNA analysis with receptor autoradiography. Int J Cancer 1997;70(5):530-7
  • Bertherat J, Tenenbaum F, Perlemoine K, et al. Somatostatin receptors 2 and 5 are the major somatostatin receptors in insulinomas: an in vivo and in vitro study. J Clin Endocrinol Metab 2003;88(11):5353-60
  • Boccardo F, Amoroso D. Management of breast cancer: is there a role for somatostatin and its analogs? Chemotherapy 2001;47(Suppl 2):62-77
  • O'Byrne KJ, Schally AV, Thomas A, et al. Somatostatin, its receptors and analogs, in lung cancer. Chemotherapy 2001;47(Suppl 2):78-108
  • Vainas IG. Octreotide in the management of hormone-refractory prostate cancer. Chemotherapy 2001;47(Suppl 2):109-26
  • Kouroumalis EA. Octreotide for cancer of the liver and biliary tree. Chemotherapy 2001;47(Suppl 2)150-61
  • Rosenberg L. Pancreatic cancer: does octreotide offer any promise? Chemotherapy 2001;47(Suppl 2):134-49
  • Smitha MC, Maggi M, Orlando C. Somatostatin receptors in non-endocrine tumours. Dig Liver Dis 2004;36(Suppl 1):S78-85
  • Reubi JC, Kvols L. Somatostatin receptors in human renal cell carcinomas. Cancer Res 1992;52(21):6074-8
  • Koutsilieris M. Pathophysiology of uterine leiomyomas. Biochem Cell Biol 1992;70(5):273-8
  • Pisarek H, Stepien T, Kubiak R, et al. Expression of somatostatin receptor subtypes in human thyroid tumors: the immunohistochemical and molecular biology (RT-PCR) investigation. Thyroid Res 2009;2(1):1
  • Pisarek H, Stepien T, Kubiak R, Pawlikowski M. Somatostatin receptors in human adrenal gland tumors–immunohistochemical study. Folia Histochem Cytobiol 2008;46(3):345-51
  • Cascinu S, Catalano V, Giordani P, et al. Gastrointestinal cancer refractory to chemotherapy: a role for octreotide? Chemotherapy 2001;47(Suppl 2):127-33
  • Kouroumalis E, Skordilis P, Thermos K, et al. Treatment of hepatocellular carcinoma with octreotide: a randomised controlled study. Gut 1998;42(3):442-7
  • Dimitroulopoulos D, Xinopoulos D, Tsamakidis K, et al. Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: randomized placebo-controlled trial. World J Gastroenterol 2007;13(23):3164-70
  • Dimopoulos MA, Kiamouris C, Gika D, et al. Combination of LHRH analog with somatostatin analog and dexamethasone versus chemotherapy in hormone-refractory prostate cancer: a randomized phase II study. Urology 2004;63(1):120-5
  • Koutsilieris M, Tzanela M, Dimopoulos T. Novel concept of antisurvival factor (ASF) therapy produces an objective clinical response in four patients with hormone-refractory prostate cancer: case report. Prostate 1999;38(4):313-6
  • Mitsiades CS, Bogdanos J, Karamanolakis D, et al. Randomized controlled clinical trial of a combination of somatostatin analog and dexamethasone plus zoledronate vs. zoledronate in patients with androgen ablation-refractory prostate cancer. Anticancer Res 2006;26(5B):3693-700
  • Mitsogiannis IC, Skolarikos A, Deliveliotis C. Somatostatin analog lanreotide in the treatment of castration-resistant prostate cancer (CRPC). Expert Opin Pharmacother 2009;10(3):493-501
  • Bauer W, Briner U, Doepfner W, et al. SMS 201-995: a very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sci 1982;31(11):1133-40
  • Eriksson B, Janson ET, Bax ND, et al. The use of new somatostatin analogues, lanreotide and octastatin, in neuroendocrine gastro-intestinal tumours. Digestion 1996;57(Suppl 1):77-80
  • Lamrani A, Vidon N, Sogni P, et al. Effects of lanreotide, a somatostatin analogue, on postprandial gastric functions and biliopancreatic secretions in humans. Br J Clin Pharmacol 1997;43(1):65-70
  • Barthomeuf C, Pourrat H, Pourrat A, et al. Stabilization of octastatin, a somatostatin analogue: comparative accelerated stability studies of two formulations for freeze-dried products. Pharm Acta Helv 1996;71(2):161-6
  • Bruns C, Raulf F, Hoyer D, et al. Binding properties of somatostatin receptor subtypes. Metabolism 1996;45(8 Suppl 1):17-20
  • Shimon I, Taylor JE, Dong JZ, et al. Somatostatin receptor subtype specificity in human fetal pituitary cultures. Differential role of SSTR2 and SSTR5 for growth hormone, thyroid-stimulating hormone, and prolactin regulation. J Clin Invest 1997;99(4):789-98
  • Reisine T, Bell GI. Molecular biology of somatostatin receptors. Endocr Rev 1995;16(4):427-42
  • Hannon JP, Nunn C, Stolz B, et al. Drug design at peptide receptors: somatostatin receptor ligands. J Mol Neurosci 2002;18(1-2):15-27
  • Lightman S. Somatuline autogel: an extended release lanreotide formulation. Hosp Med 2002;63(3):162-5
  • Anthony LB. Long-acting formulations of somatostatin analogues. Ital J Gastroenterol Hepatol 1999;31(Suppl 2):S216-8
  • McKeage K, Cheer S, Wagstaff AJ. Octreotide long-acting release (LAR): a review of its use in the management of acromegaly. Drugs 2003;63(22):2473-99
  • Vallette S, Serri O. Octreotide LAR for the treatment of acromegaly. Expert Opin Drug Metab Toxicol 2008;4(6):783-93
  • Rothen-Weinhold A, Besseghir K, De Zelicourt Y, Gurny R. Development and evaluation in vivo of a long-term delivery system for vapreotide, a somatostatin analogue. J Control Release 1998;52(1-2):205-13
  • Attanasio R, Lanzi R, Losa M, et al. Effects of lanreotide autogel on growth hormone, insulinlike growth factor 1, and tumor size in acromegaly: a 1-year prospective multicenter study. Endocr Pract 2008;14(7):846-55
  • Norman P. Vapreotide (Debipharm). IDrugs 2000;3(11):1358-72
  • Cales P. Vapreotide acetate for the treatment of esophageal variceal bleeding. Expert Rev Gastroenterol Hepatol 2008;2(2):185-92
  • Schmid HA. Pasireotide (SOM230): development, mechanism of action and potential applications. Mol Cell Endocrinol 2008;286(1-2):69-74
  • Bruns C, Lewis I, Briner U, et al. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 2002;146(5):707-16
  • Lewis I, Bauer W, Albert R, et al. A novel somatostatin mimic with broad somatotropin release inhibitory factor receptor binding and superior therapeutic potential. J Med Chem 2003;46(12):2334-44
  • Lesche S, Lehmann D, Nagel F, et al. Differential effects of octreotide and pasireotide on somatostatin receptor internalization and trafficking in vitro. J Clin Endocrinol Metab 2009;94(2):654-61
  • Batista DL, Zhang X, Gejman R, et al. The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas. J Clin Endocrinol Metab 2006;91(11):4482-8
  • Ma P, Wang Y, van der Hoek J, et al. Pharmacokinetic-pharmacodynamic comparison of a novel multiligand somatostatin analog, SOM230, with octreotide in patients with acromegaly. Clin Pharmacol Ther 2005;78(1):69-80
  • van der Hoek J, van der Lelij AJ, Feelders RA, et al. The somatostatin analogue SOM230, compared with octreotide, induces differential effects in several metabolic pathways in acromegalic patients. Clin Endocrinol (Oxf) 2005;63(2):176-84
  • Kvols L, Wiedenmann B, Oberg K, et al. Safety and efficacy of pasireotide (SOM230) in patients with metastatic carcinoid tumors refractory or resistant to octreotide LAR: results of a phase II study. J Clin Oncol 2006;24:198s
  • Farrall AJ, Glusman JE, Ruffin M, Petersenn S. Pasireotide (SOM230) effectively reduces pituitary tumor volume in patients with active acromegaly: preliminary 6-month results from a phase II extension study. In: ENDO [abstract OR53-4]; 2007
  • Msaouel P, Diamanti E, Tzanela M, Koutsilieris M. Luteinising hormone-releasing hormone antagonists in prostate cancer therapy. Expert Opin Emerg Drugs 2007;12(2):285-99
  • Msaouel P, Nixon AM, Bramos AP, et al. Extracellular calcium sensing receptor: an overview of physiology, pathophysiology and clinical perspectives. In Vivo 2004;18(6):739-53
  • Bass RT, Buckwalter BL, Patel BP, et al. Identification and characterization of novel somatostatin antagonists. Mol Pharmacol 1996;50(4):709-15
  • van der Hoek J, Hofland LJ, Lamberts SW. Novel subtype specific and universal somatostatin analogues: clinical potential and pitfalls. Curr Pharm Des 2005;11(12):1573-92
  • Ginj M, Zhang H, Waser B, et al. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. Proc Natl Acad Sci USA 2006;103(44):16436-41
  • Wolkenberg SE, Thut CJ. Recent progress in the discovery of selective, non-peptide ligands of somatostatin receptors. Curr Opin Drug Discov Devel 2008;11(4):446-57
  • van der Hoek J, Lamberts SW, Hofland LJ. Preclinical and clinical experiences with the role of somatostatin receptors in the treatment of pituitary adenomas. Eur J Endocrinol 2007;156(Suppl 1):S45-51
  • Murray RD, Melmed S. A critical analysis of clinically available somatostatin analog formulations for therapy of acromegaly. J Clin Endocrinol Metab 2008;93(8):2957-68
  • Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ. Octreotide. N Engl J Med 1996;334(4):246-54
  • de Herder WW, Lamberts SW. Clinical endocrinology and metabolism. Gut endocrine tumours. Best Pract Res Clin Endocrinol Metab 2004;18(4):477-95
  • Oberg K. Established clinical use of octreotide and lanreotide in oncology. Chemotherapy 2001;47(Suppl 2):40-53
  • Patel YC. Molecular pharmacology of somatostatin receptor subtypes. J Endocrinol Invest 1997;20(6):348-67
  • Hofland LJ, Lamberts SW. The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocr Rev 2003;24(1):28-47
  • Jacobs S, Schulz S. Intracellular trafficking of somatostatin receptors. Mol Cell Endocrinol 2008;286(1-2):58-62
  • Roosterman D, Kempkes C, Cottrell GS, et al. Endothelin-converting enzyme-1 degrades internalized somatostatin-14. Endocrinology 2008;149(5):2200-7
  • Pfeiffer M, Koch T, Schroder H, et al. Homo- and heterodimerization of somatostatin receptor subtypes. Inactivation of sst(3) receptor function by heterodimerization with sst(2A). J Biol Chem 2001;276(17):14027-36
  • Florio T. Molecular mechanisms of the antiproliferative activity of somatostatin receptors (SSTRs) in neuroendocrine tumors. Front Biosci 2008;13:822-40
  • Olias G, Viollet C, Kusserow H, et al. Regulation and function of somatostatin receptors. J Neurochem 2004;89(5):1057-91
  • Alderton F, Humphrey PP, Sellers LA. High-intensity p38 kinase activity is critical for p21(cip1) induction and the antiproliferative function of G(i) protein-coupled receptors. Mol Pharmacol 2001;59(5):1119-28
  • Ferjoux G, Bousquet C, Cordelier P, et al. Signal transduction of somatostatin receptors negatively controlling cell proliferation. J Physiol Paris 2000;94(3-4):205-10
  • Bousquet C, Delesque N, Lopez F, et al. sst2 somatostatin receptor mediates negative regulation of insulin receptor signaling through the tyrosine phosphatase SHP-1. J Biol Chem 1998;273(12):7099-106
  • Massa A, Barbieri F, Aiello C, et al. The expression of the phosphotyrosine phosphatase DEP-1/PTPeta dictates the responsivity of glioma cells to somatostatin inhibition of cell proliferation. J Biol Chem 2004;279(28):29004-12
  • Cordelier P, Esteve JP, Bousquet C, et al. Characterization of the antiproliferative signal mediated by the somatostatin receptor subtype sst5. Proc Natl Acad Sci USA 1997;94(17):9343-8
  • Florio T, Yao H, Carey KD, et al. Somatostatin activation of mitogen-activated protein kinase via somatostatin receptor 1 (SSTR1). Mol Endocrinol 1999;13(1):24-37
  • Lahlou H, Saint-Laurent N, Esteve JP, et al. sst2 Somatostatin receptor inhibits cell proliferation through Ras-, Rap1-, and B-Raf-dependent ERK2 activation. J Biol Chem 2003;278(41):39356-71
  • Papageorgiou E, Pitulis N, Msaouel P, et al. The non-genomic crosstalk between PPAR-gamma ligands and ERK1/2 in cancer cell lines. Expert Opin Ther Targets 2007;11(8):1071-85
  • Roovers K, Assoian RK. Integrating the MAP kinase signal into the G1 phase cell cycle machinery. Bioessays 2000;22(9):818-26
  • Sellers LA, Feniuk W, Humphrey PP, Lauder H. Activated G protein-coupled receptor induces tyrosine phosphorylation of STAT3 and agonist-selective serine phosphorylation via sustained stimulation of mitogen-activated protein kinase. Resultant effects on cell proliferation. J Biol Chem 1999;274(23):16423-30
  • Sellers LA, Alderton F, Carruthers AM, et al. Receptor isoforms mediate opposing proliferative effects through gbetagamma-activated p38 or Akt pathways. Mol Cell Biol 2000;20(16):5974-85
  • Theodoropoulou M, Zhang J, Laupheimer S, et al. Octreotide, a somatostatin analogue, mediates its antiproliferative action in pituitary tumor cells by altering phosphatidylinositol 3-kinase signaling and inducing Zac1 expression. Cancer Res 2006;66(3):1576-82
  • Grozinsky-Glasberg S, Franchi G, Teng M, et al. Octreotide and the mTOR inhibitor RAD001 (everolimus) block proliferation and interact with the Akt-mTOR-p70S6K pathway in a neuro-endocrine tumour cell Line. Neuroendocrinology 2008;87(3):168-81
  • Sharma K, Srikant CB. Induction of wild-type p53, Bax, and acidic endonuclease during somatostatin-signaled apoptosis in MCF-7 human breast cancer cells. Int J Cancer 1998;76(2):259-66
  • Srikant CB. Cell cycle dependent induction of apoptosis by somatostatin analog SMS 201-995 in AtT-20 mouse pituitary cells. Biochem Biophys Res Commun 1995;209(2):400-6
  • 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(12):1688-96
  • 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(4):1574-84
  • Teijeiro R, Rios R, Costoya JA, et al. Activation of human somatostatin receptor 2 promotes apoptosis through a mechanism that is independent from induction of p53. Cell Physiol Biochem 2002;12(1):31-8
  • Ferrante E, Pellegrini C, Bondioni S, et al. Octreotide promotes apoptosis in human somatotroph tumor cells by activating somatostatin receptor type 2. Endocr Relat Cancer 2006;13(3):955-62
  • Msaouel P, Pissimissis N, Halapas A, Koutsilieris M. Mechanisms of bone metastasis in prostate cancer: clinical implications. Best Pract Res Clin Endocrinol Metab 2008;22(2):341-55
  • Susini C, Buscail L. Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol 2006;17(12):1733-42
  • Serri O, Brazeau P, Kachra Z, Posner B. Octreotide inhibits insulin-like growth factor-I hepatic gene expression in the hypophysectomized rat: evidence for a direct and indirect mechanism of action. Endocrinology 1992;130(4):1816-21
  • Pokrajac A, Frystyk J, Flyvbjerg A, Trainer PJ. Pituitary-independent effect of octreotide on IGF-I generation. Eur J Endocrinol 2009;160(4):543-8
  • Cervia D, Bagnoli P. An update on somatostatin receptor signaling in native systems and new insights on their pathophysiology. Pharmacol Ther 2007;116(2):322-41
  • Tallent M, Liapakis G, O'Carroll AM, et al. Somatostatin receptor subtypes SSTR2 and SSTR5 couple negatively to an L-type Ca2+ current in the pituitary cell line AtT-20. Neuroscience 1996;71(4):1073-81
  • Roosterman D, Glassmeier G, Baumeister H, et al. A somatostatin receptor 1 selective ligand inhibits Ca2+ currents in rat insulinoma 1046-38 cells. FEBS Lett 1998;425(1):137-40
  • Lahlou H, Fanjul M, Pradayrol L, et al. Restoration of functional gap junctions through internal ribosome entry site-dependent synthesis of endogenous connexins in density-inhibited cancer cells. Mol Cell Biol 2005;25(10):4034-45
  • Koutsilieris M. Skeletal metastases in advanced prostate cancer: cell biology and therapy. Crit Rev Oncol Hematol 1995;18(1):51-64
  • Gastpar H, Zoltobrocki M, Weissgerber PW. The inhibition of cancer cell stickiness by somatostatin. Res Exp Med (Berl) 1983;182(1):1-6
  • Friend KE. Targeting the growth hormone axis as a therapeutic strategy in oncology. Growth Horm IGF Res 2000;10(Suppl A):S45-6
  • Laban C, Bustin SA, Jenkins PJ. The GH-IGF-I axis and breast cancer. Trends Endocrinol Metab 2003;14(1):28-34
  • Macaulay VM. Insulin-like growth factors and cancer. Br J Cancer 1992;65(3):311-20
  • Pollak MN, Schally AV. Mechanisms of antineoplastic action of somatostatin analogs. Proc Soc Exp Biol Med 1998;217(2):143-52
  • Ambler GR, Butler AA, Padmanabhan J, et al. The effects of octreotide on GH receptor and IGF-I expression in the GH-deficient rat. J Endocrinol 1996;149(2):223-31
  • Koutsilieris M, Polychronakos C. Proteinolytic activity against IGF-binding proteins involved in the paracrine interactions between prostate adenocarcinoma cells and osteoblasts. Anticancer Res 1992;12(3):905-10
  • Ezzat S, Ren SG, Braunstein GD, Melmed S. Octreotide stimulates insulin-like growth factor binding protein-1 (IGFBP-1) levels in acromegaly. J Clin Endocrinol Metab 1991;73(2):441-3
  • Ren SG, Ezzat S, Melmed S, Braunstein GD. Somatostatin analog induces insulin-like growth factor binding protein-1 (IGFBP-1) expression in human hepatoma cells. Endocrinology 1992;131(5):2479-81
  • Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86(3):353-64
  • Charlesworth PJ, Harris AL. Mechanisms of disease: angiogenesis in urologic malignancies. Nat Clin Pract Urol 2006;3(3):157-69
  • Chiang AC, Massague J. Molecular basis of metastasis. N Engl J Med 2008;359(26):2814-23
  • Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003;3(6):401-10
  • Fujita Y, Abe R, Shimizu H. Clinical approaches toward tumor angiogenesis: past, present and future. Curr Pharm Des 2008;14(36):3820-34
  • Hemingway DM, Jenkins SA, Cooke TG. The effects of sandostatin (Octreotide, SMS 201-995) infusion on splanchnic and hepatic blood flow in an experimental model of hepatic metastases. Br J Cancer 1992;65(3):396-8
  • Davies N, Yates J, Kynaston H, et al. Effects of octreotide on liver regeneration and tumour growth in the regenerating liver. J Gastroenterol Hepatol 1997;12(1):47-53
  • Davies N, Kynaston H, Yates J, et al. Octreotide inhibits the growth and development of three types of experimental liver metastases. Br J Surg 1995;82(6):840-3
  • Davies N, Kynaston H, Yates J, et al. Octreotide, the reticuloendothelial system, and experimental liver tumour. Gut 1995;36(4):610-4
  • Albini A, Florio T, Giunciuglio D, et al. Somatostatin controls Kaposi's sarcoma tumor growth through inhibition of angiogenesis. FASEB J 1999;13(6):647-55
  • Curtis SB, Hewitt J, Yakubovitz S, et al. Somatostatin receptor subtype expression and function in human vascular tissue. Am J Physiol Heart Circ Physiol 2000;278(6):H1815-22
  • Wang C, Tang C. Inhibition of human gastric cancer metastasis by ocreotide in vitro and in vivo. Zhonghua Yi Xue Za Zhi 2002;82(1):19-22
  • Dasgupta P. Somatostatin analogues: multiple roles in cellular proliferation, neoplasia, and angiogenesis. Pharmacol Ther 2004;102(1):61-85
  • Jia WD, Xu GL, Xu RN, et al. Octreotide acts as an antitumor angiogenesis compound and suppresses tumor growth in nude mice bearing human hepatocellular carcinoma xenografts. J Cancer Res Clin Oncol 2003;129(6):327-34
  • Adams RL, Adams IP, Lindow SW, et al. Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium. Br J Cancer 2005;92(8):1493-8
  • Adams RL, Adams IP, Lindow SW, Atkin SL. Inhibition of endothelial proliferation by the somatostatin analogue SOM230. Clin Endocrinol (Oxf) 2004;61(4):431-6
  • Buchan AM, Lin CY, Choi J, Barber DL. Somatostatin, acting at receptor subtype 1, inhibits Rho activity, the assembly of actin stress fibers, and cell migration. J Biol Chem 2002;277(32):28431-8
  • Li HH, Wang XC, Lu JR, et al. Effects of short-term treatment of somatostatin on angiogenesis of gastric carcinoma. Ai Zheng 2003;22(9):990-3
  • Ferone D, van Hagen PM, Semino C, et al. Somatostatin receptor distribution and function in immune system. Dig Liver Dis 2004;36(Suppl 1):S68-77
  • Pinter E, Helyes Z, Szolcsanyi J. Inhibitory effect of somatostatin on inflammation and nociception. Pharmacol Ther 2006;112(2):440-56
  • Wiedermann CJ, Reinisch N, Braunsteiner H. Stimulation of monocyte chemotaxis by human growth hormone and its deactivation by somatostatin. Blood 1993;82(3):954-60
  • McLean K, Buckanovich RJ. Myeloid cells functioning in tumor vascularization as a novel therapeutic target. Transl Res 2008;151(2):59-67
  • Sirianni MC, Annibale B, Fais S, Delle Fave G. Inhibitory effect of somatostatin-14 and some analogues on human natural killer cell activity. Peptides 1994;15(6):1033-6
  • Pawlikowski M, Zelazowski P, Stepien H. Enhancement of human lymphocyte natural killer activity by somatostatin. Neuropeptides 1989;13(2):75-7
  • Dean A. The palliative effects of octreotide in cancer patients. Chemotherapy 2001;47(Suppl 2):54-61
  • Norheim I, Oberg K, Theodorsson-Norheim E, et al. Malignant carcinoid tumors. An analysis of 103 patients with regard to tumor localization, hormone production, and survival. Ann Surg 1987;206(2):115-25
  • Feldman JM. Carcinoid tumors and syndrome. Semin Oncol 1987;14(3):237-46
  • de Herder WW, Lamberts SW. Somatostatin analog therapy in treatment of gastrointestinal disorders and tumors. Endocrine 2003;20(3):285-90
  • Smith S, Anthony L, Roberts LJ, et al. Resolution of musculoskeletal symptoms in the carcinoid syndrome after treatment with the somatostatin analog octreotide. Ann Intern Med 1990;112(1):66-8
  • Mollenholt P, Rawal N, Gordh T Jr, Olsson Y. Intrathecal and epidural somatostatin for patients with cancer. Analgesic effects and postmortem neuropathologic investigations of spinal cord and nerve roots. Anesthesiology 1994;81(3):534-42
  • Penn RD, Paice JA, Kroin JS. Octreotide: a potent new non-opiate analgesic for intrathecal infusion. Pain 1992;49(1):13-9
  • Paice JA, Penn RD, Kroin JS. Intrathecal octreotide for relief of intractable nonmalignant pain: 5-year experience with two cases. Neurosurgery 1996;38(1):203-7
  • Tan AD, Novotny PJ, Kaur JS, et al. A patient-level meta-analytic investigation of the prognostic significance of baseline quality of life (QOL) for overall survival (OS) among 3,704 patients participating in 24 North Central Cancer Treatment Group (NCCTG) and Mayo Clinic Cancer Center (MC) oncology clinical trials. J Clin Oncol 2008;20(suppl):abstract 9515
  • Balon HR, Goldsmith SJ, Siegel BA, et al. Procedure guideline for somatostatin receptor scintigraphy with (111)In-pentetreotide. J Nucl Med 2001;42(7):1134-8
  • Krenning EP, Bakker WH, Kooij PP, et al. Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. J Nucl Med 1992;33(5):652-8
  • Janson ET, Westlin JE, Ohrvall U, et al. Nuclear localization of 111In after intravenous injection of [111In-DTPA-D-Phe1]-octreotide in patients with neuroendocrine tumors. J Nucl Med 2000;41(9):1514-8
  • Papotti M, Croce S, Bello M, et al. Expression of somatostatin receptor types 2, 3 and 5 in biopsies and surgical specimens of human lung tumours. Correlation with preoperative octreotide scintigraphy. Virchows Arch 2001;439(6):787-97
  • Vekemans MC, Urbain JL, Charkes D. Advances in radio-imaging of neuroendocrine tumors. Curr Opin Oncol 1995;7(1):63-7
  • de Herder WW, Kwekkeboom DJ, Feelders RA, et al. Somatostatin receptor imaging for neuroendocrine tumors. Pituitary 2006;9(3):243-8
  • Reubi JC, Schar JC, Waser B, et al. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 2000;27(3):273-82
  • Smith-Jones PM, Bischof C, Leimer M, et al. DOTA-lanreotide: a novel somatostatin analog for tumor diagnosis and therapy. Endocrinology 1999;140(11):5136-48
  • Virgolini I, Leimer M, Handmaker H, et al. Somatostatin receptor subtype specificity and in vivo binding of a novel tumor tracer, 99mTc-P829. Cancer Res 1998;58(9):1850-9
  • Mitsiades C, Bogdanos J, Karamanolakis D, et al. Bone microenvironment participation in the development of androgen ablation in prostate cancer patients with bone metastases: clinical application of an anti-survival factor therapy. In: Labrie F, et al., editors, Prostate cancer: understanding the pathophysiology and re-designing a therapeutic approach. Paschalidis Medical Publications, Athens; 2004. p. 109-34
  • Mitsiades CS, Koutsilieris M. Molecular biology and cellular physiology of refractoriness to androgen ablation therapy in advanced prostate cancer. Expert Opin Investig Drugs 2001;10(6):1099-115
  • Koutsilieris M, Sourla A, Pelletier G, Doillon CJ. Three-dimensional type I collagen gel system for the study of osteoblastic metastases produced by metastatic prostate cancer. J Bone Miner Res 1994;9(11):1823-32
  • Bogdanos J, Karamanolakis D, Tenta R, et al. Endocrine/paracrine/autocrine survival factor activity of bone microenvironment participates in the development of androgen ablation and chemotherapy refractoriness of prostate cancer metastasis in skeleton. Endocr Relat Cancer 2003;10(2):279-89
  • Koutsilieris M, Reyes-Moreno C, Sourla A, et al. Growth factors mediate glucocorticoid receptor function and dexamethasone-induced regression of osteoblastic lesions in hormone refractory prostate cancer. Anticancer Res 1997;17(3A):1461-5
  • Kruit A, Reyes-Moreno C, Newling DW, et al. Response of PC-3 prostate cancer cells to combination therapy using irradiation with glucocorticoids or doxorubicin. Anticancer Res 1999;19(4B):3153-6
  • Reyes-Moreno C, Koutsilieris M. Glucocorticoid receptor function possibly modulates cell-cell interactions in osteoblastic metastases on rat skeleton. Clin Exp Metastasis 1997;15(3):205-17
  • Koutsilieris M, Bogdanos J, Milathianakis C, et al. Combination therapy using LHRH and somatostatin analogues plus dexamethasone in androgen ablation refractory prostate cancer patients with bone involvement: a bench to bedside approach. Expert Opin Investig Drugs 2006;15(7):795-804
  • Koutsilieris M, Dimopoulos T, Milathianakis C, et al. Combination of somatostatin analogues and dexamethasone (anti-survival-factor concept) with luteinizing hormone-releasing hormone in androgen ablation-refractory prostate cancer with bone metastasis. BJU Int 2007;100(Suppl 2):60-2
  • Schally AV. Luteinizing hormone-releasing hormone analogs: their impact on the control of tumorigenesis. Peptides 1999;20(10):1247-62
  • Tolis G, Faure N, Koutsilieris M, et al. Suppression of testicular steroidogenesis by the GnRH agonistic analogue buserelin (HOE-766) in patients with prostatic cancer: studies in relation to dose and route of administration. J Steroid Biochem 1983;19(1C):995-8
  • Tenta R, Sourla A, Lembessis P, et al. Bone microenvironment-related growth factors, zoledronic acid and dexamethasone differentially modulate PTHrP expression in PC-3 prostate cancer cells. Horm Metab Res 2005;37(10):593-601
  • Reyes-Moreno C, Sourla A, Choki I, et al. Osteoblast-derived survival factors protect PC-3 human prostate cancer cells from adriamycin apoptosis. Urology 1998;52(2):341-7
  • Koutsilieris M, Tenta R, Tiblalexi D, et al. Bone metastasis microenvironment participates in the development of androgen ablation refractoriness and chemotherapy resistance of prostate cancer cells residing in the skeleton: clinical implications. In: Meadows G editor, Integration/interaction of oncologic growth. Springer; 2005. p. 335-44
  • Reyes-Moreno C, Frenette G, Boulanger J, et al. Mediation of glucocorticoid receptor function by transforming growth factor beta I expression in human PC-3 prostate cancer cells. Prostate 1995;26(5):260-9
  • Koutsilieris M, Mitsiades C, Dimopoulos T, et al. A combination therapy of dexamethasone and somatostatin analog reintroduces objective clinical responses to LHRH analog in androgen ablation-refractory prostate cancer patients. J Clin Endocrinol Metab 2001;86(12):5729-36
  • Koutsilieris M, Mitsiades CS, Bogdanos J, et al. Combination of somatostatin analog, dexamethasone, and standard androgen ablation therapy in stage D3 prostate cancer patients with bone metastases. Clin Cancer Res 2004;10(13):4398-405
  • Silva F, Da Silva F, Goncalves F, Oliver T. South European Uroncological Group: Phase II screening study to assess the combination of a LHRH analogue, dexamethasone and a somatostatin analogue versus a LHRH analogue with dexamethasone in hormone refractory prostate cancer patients. J Clin Oncol, 2006 ASCO Annual Meeting Proceedings Part I 2006;24(18S):4565
  • Di Silverio F, Sciarra A. Combination therapy of ethinylestradiol and somatostatin analogue reintroduces objective clinical responses and decreases chromogranin a in patients with androgen ablation refractory prostate cancer. J Urol 2003;170(5):1812-6
  • Kaltsas GA, Papadogias D, Makras P, Grossman AB. Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues. Endocr Relat Cancer 2005;12(4):683-99
  • Kwekkeboom DJ, Teunissen JJ, Kam BL, et al. Treatment of patients who have endocrine gastroenteropancreatic tumors with radiolabeled somatostatin analogues. Hematol Oncol Clin North Am 2007;21(3):561-73; x
  • Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008;26(13):2124-30
  • Nagy A, Schally AV, Halmos G, et al. Synthesis and biological evaluation of cytotoxic analogs of somatostatin containing doxorubicin or its intensely potent derivative, 2-pyrrolinodoxorubicin. Proc Natl Acad Sci USA 1998;95(4):1794-9
  • Nagy A, Schally AV. Targeting cytotoxic conjugates of somatostatin, luteinizing hormone-releasing hormone and bombesin to cancers expressing their receptors: a “smarter” chemotherapy. Curr Pharm Des 2005;11(9):1167-80
  • Nagy A, Armatis P, Schally AV. High yield conversion of doxorubicin to 2-pyrrolinodoxorubicin, an analog 500-1000 times more potent: structure-activity relationship of daunosamine-modified derivatives of doxorubicin. Proc Natl Acad Sci USA 1996;93(6):2464-9
  • Engel JB, Schally AV, Halmos G, et al. Targeted therapy with a cytotoxic somatostatin analog, AN-238, inhibits growth of human experimental endometrial carcinomas expressing multidrug resistance protein MDR-1. Cancer 2005;104(6):1312-21
  • Keller G, Schally AV, Nagy A, et al. Effective therapy of experimental human malignant melanomas with a targeted cytotoxic somatostatin analogue without induction of multi-drug resistance proteins. Int J Oncol 2006;28(6):1507-13
  • Kidd M, Schally AV, Pfragner R, et al. Inhibition of proliferation of small intestinal and bronchopulmonary neuroendocrine cell lines by using peptide analogs targeting receptors. Cancer 2008;112(6):1404-14
  • Szepeshazi K, Schally AV, Treszl A, et al. Therapy of experimental hepatic cancers with cytotoxic peptide analogs targeted to receptors for luteinizing hormone-releasing hormone, somatostatin or bombesin. Anticancer Drugs 2008;19(4):349-58
  • Keller G, Engel JB, Schally AV, et al. Growth inhibition of experimental non-hodgkin's lymphomas with the targeted cytotoxic somatostatin analogue AN-238. Int J Cancer 2005;114(5):831-5
  • Buchholz S, Keller G, Schally AV, et al. Therapy of ovarian cancers with targeted cytotoxic analogs of bombesin, somatostatin, and luteinizing hormone-releasing hormone and their combinations. Proc Natl Acad Sci USA 2006;103(27):10403-7
  • Nagy A, Plonowski A, Schally AV. Stability of cytotoxic luteinizing hormone-releasing hormone conjugate (AN-152) containing doxorubicin 14-O-hemiglutarate in mouse and human serum in vitro: implications for the design of preclinical studies. Proc Natl Acad Sci USA 2000;97(2):829-34
  • Kiaris H, Schally AV, Nagy A, et al. A targeted cytotoxic somatostatin (SST) analogue, AN-238, inhibits the growth of H-69 small-cell lung carcinoma (SCLC) and H-157 non-SCLC in nude mice. Eur J Cancer 2001;37(5):620-8
  • Plonowski A, Schally AV, Nagy A, et al. Inhibition of PC-3 human androgen-independent prostate cancer and its metastases by cytotoxic somatostatin analogue AN-238. Cancer Res 1999;59(8):1947-53
  • Eriksson B, Renstrup J, Imam H, Oberg K. High-dose treatment with lanreotide of patients with advanced neuroendocrine gastrointestinal tumors: clinical and biological effects. Ann Oncol 1997;8(10):1041-4
  • Anthony L, Johnson D, Hande K, et al. Somatostatin analogue phase I trials in neuroendocrine neoplasms. Acta Oncol 1993;32(2):217-23
  • Faiss S, Rath U, Mansmann U, et al. Ultra-high-dose lanreotide treatment in patients with metastatic neuroendocrine gastroenteropancreatic tumors. Digestion 1999;60(5):469-76
  • Ferone D, Gatto F, Arvigo M, et al. The clinical-molecular interface of somatostatin, dopamine and their receptors in pituitary pathophysiology. J Mol Endocrinol 2009;42(5):361-70

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.