Elevated Expression of Galanin Receptors in Childhood Neuroblastic TumorsBerger A.a · Tuechler C.a · Almer D.a · Kogner P.b · Ratschek M.c · Kerbl R.d · Iismaa T.P.e · Jones N.a · Sperl W.a · Kofler B.a
aDepartment of Pediatrics, General Hospital Salzburg, Salzburg, Austria; bChildhood Cancer Research Unit, Astrid Lindgren Children’s Hospital, Stockholm, Sweden; Institutes of cPathology and dPediatrics, University of Graz, Austria; eGarvan Institute of Medical Research, Sydney, N.S.W., Australia
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The neuropeptide galanin (GAL) has been shown to be present in certain brain tumors. In order to learn more about GAL and its receptors in human tumors of the peripheral nervous system, we investigated the expression of the GAL peptide and the GAL receptors in tumor tissue from childhood neuroblastic tumors. GAL peptide concentrations up to 674 ± 166 fmol/mg of tissue were detected by radioimmunoassay, but no significant correlation with standard tumor markers or the prognosis of the 14 patients investigated was observed. Ligand binding experiments showed different levels of GAL binding in all 28 primary neuroblastomas and 7 ganglioneuromas investigated. All three human GAL receptor subtypes cloned to date could be detected, with the GALR1 receptor subtype being expressed most prominently. GAL binding did not significantly correlate with genetic markers such as unfavorable DNA ploidy, amplification of the oncogene MYCN and allelic loss of chromosome 1p. However, low galanin binding was significantly correlated with survival (p = 0.021) in this limited analysis of neuroblastic tumor samples. These results raise the possibility that the expression of GAL binding sites may play a role in neuroblastic tumor biology and behavior.
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- Tatemoto K, Rökaeus A, Jörnvall H, McDonald TJ, Mutt V: Galanin – a novel biologically active peptide from porcine intestine. FEBS Lett 1983;164:124–128.
- Kordower JH, Le HK, Mufson EJ: Galanin immunoreactivity in the primate central nervous system. J Comp Neurol 1992;319:479–500.
- Giustina A, Licini M, Schettino M, Doga M, Pizzocolo G, Negro-Vilar A: Physiological role of galanin in the regulation of anterior pituitary function in humans. Am J Physiol 1994;266:E57–E61.
- Lopez FJ, Merchenthaler I, Liposits Z, Negro-Vilar A: Steroid imprinting and modulation of sexual dimorphism in the luteinizing hormone-releasing hormone neuronal system. Cell Mol Neurobiol 1996;16:129–141.
- Wynick D, Hammond PJ, Akinsanya KO, Bloom SR: Galanin regulates basal and oestrogen-stimulated lactotroph function. Nature 1993;364:529–532.
- Sethi T, Rozengurt E: Multiple neuropeptides stimulate clonal growth of small cell lung cancer: Effects of bradykinin, vasopressin, cholecystokinin, galanin, and neurotensin. Cancer Res 1991;51:3621–3623.
- Sethi T, Rozengurt E: Galanin stimulates Ca2+ mobilization, inositol phosphate accumulation, and clonal growth in small cell lung cancer cells. Cancer Res 1991;51:1674–1679.
- Vrontakis ME, Sano T, Kovacs K, Friesen HG: Presence of galanin-like immunoreactivity in nontumorous corticotrophs and corticotroph adenomas of the human pituitary. J Clin Endocrinol Metab 1990;70:747–751.
- Sano T, Vrontakis ME, Kovacs K, Asa SL, Friesen HG: Galanin immunoreactivity in neuroendocrine tumors. Arch Pathol Lab Med 1991;115:926–929.
- Bauer FE, Hacker GW, Terenghi G, Adrian TE, Polak JM, Bloom SR: Localization and molecular forms of galanin in human adrenals: Elevated levels in pheochromocytomas. J Clin Endocrinol Metab 1986;63:1372–1378.
- Habert-Ortoli E, Amiranoff B, Loquet I, Laburthe M, Mayaux JF: Molecular cloning of a functional human galanin receptor. Proc Natl Acad Sci USA 1994;91:9780–9783.
- Fathi Z, Battaglino P, Iben L, Li H, Baker E, Zhang D, McGovern R, Mahle C, Sutherland G, Iismaa TP, Dickinson K, Zimanyi AI: Molecular characterization, pharmacological properties and chromosomal localization of the human GALR2 galanin receptor. Brain Res Mol Brain Res 1998;58:156–169.
- Kolakowski LF, O’Neill GP, Howard AD, Broussard SR, Sullivan KA, Feighner SD, Sawzdargo M, Nguyen T, Kargman S, Shiao LL, Hreniuk DL, Tan CP, Evans J, Abramovitz M, Chateauneuf A, Coulombe N, Ng G, Johnson MP, Tharian A, Khoshbouei H, George SR, Smith RG, O’Dowd BF: Molecular characterization and expression of cloned human galanin receptors GALR2 and GALR3. J Neurochem 1998;71:2239–2251.
- Hulting AL, Land T, Berthold M, Langel U, Hokfelt T, Bartfai T: Galanin receptors from human pituitary tumors assayed with human galanin as ligand. Brain Res 1993;625:173–176.
Reubi J, Schaer J, Markwalder R, Waser B, Horisberger U, Laissue J: Distribution of somatostatin receptors in normal and neoplastic human tissues: Recent advances and potential relevance. Yale J Biol Med 1997;70:471–479.
- Reubi J, Waser B, Schaer J, Laissue J: Neurotensin receptors in human neoplasms: High incidence in Ewing’s sarcoma. Int J Cancer 1999;82:213–218.
- Sestini R, Orlando C, Peri A, Tricarico C, Pazzagli M, Serio M, Pagani A, Bussolati G, Granchi S, Maggi M: Quantitation of somatostatin receptor type 2 gene expression in neuroblastoma cell lines and primary tumors using competitive reverse transcription-polymerase chain reaction. Clin Cancer Res 1996;2:1757–1765.
Ambros PF, Ambros IM, Ladensteiner R, Gadner H: Neuroblastoma: Impact of biological characteristics on treatment strategies. Onkologie 1995;18:548–555.
- Ambros IM, Zellner A, Roald B, Amann G, Ladenstein R, Printz D, Gadner H, Ambros PF: Role of ploidy, chromosome 1p, and Schwann cells in the maturation of neuroblastoma. N Engl J Med 1996;334:1505–1511.
- Look A, Hayes F, Shuster J, Douglass H, Castelberry R, Bowman L, Smith I, Brodeur G: Clinical relevance of tumor cell ploidy, N-myc gene amplification in childhood neuroblastoma: A Pediatric Oncology Group Study. J Clin Oncol 1991;9:581–591.
- Rubie H, Hartmann O, Michon J, Frappaz D, Coze C, Chastanger P, Baranzelli M, Plantaz D, Avet-Loiseau H, Benard J, Delattre O, Favrot M, Peyroulet M, Thyss A, Perel Y, Bergeron C, Coubon-Collet B, Vannier J, Lemerle J, Sommelet D: N-myc gene amplification is a major prognostic factor in localized neuroblastoma: Results of the French NBL 90 study. Neuroblastoma Study Group of the Société Française d’Oncologie Pédiatrique. J Clin Oncol 1997;15:1171–1182.
- Tsuchida Y, Hemmi H, Inoue A, Obana K, Yang HW, Hayashi Y, Kanda N, Shimatake H: Genetic clinical markers of human neuroblastoma with special reference to N-myc oncogene: Amplified or not amplified? An overview. Tumor Biol 1996;17:65–74.
- Caron H, van Sluis P, de Kraker J, Bokkerink J, Egeler M, Laureys G, Slater R, Westerveld A, Voute PA, Versteeg R: Allelic loss of chromosome 1p as a predictor of unfavorable outcome in patients with neuroblastoma. N Engl J Med 1996;334:225–230.
- Brown N, Cotterill S, Lastowska M, O’Neill S, Pearson ADJ, Plantaz D, Meddeb M, Danglot G, Brinkschmidt C, Christiansen H, Laureys G, Speleman F: Gain of chromosome 17q and adverse outcome in patients with neuroblastoma. N Engl J Med 1999;340:1954–1961.
- Nakagawara A, Arima-Nakagawara M, Scavarda NJ, Azar CG, Cantor AB, Brodeur GM: Association between high levels of expression of the TRK gene and favorable outcome in human neuroblastoma. N Engl J Med 1993;328:847–854.
- Kogner P, Barbany G, Dominici C, Castello M, Raschella G, Persson H: Coexpression of messenger RNA for trk protooncogene and low affinity nerve growth factor receptor in neuroblastoma with favorable prognosis. Cancer Res 1993;53:2044–2050.
- Norris MD, Bordow SB, Marshall GM, Haber PS, Cohn SL, Haber M: Expression of the gene for multidrug-resistance-associated protein and outcome in patients with neuroblastoma. N Engl J Med 1996;334:231–238.
- Raschella G, Cesi V, Amendola R, Negroni A, Tanno B, Altavista P, Tonnini G, De Bernardi B, Calabretta B: Expression of B-myb in neuroblastoma tumors is a poor prognostic factor independent from MYCN amplification. Cancer Res 1999;59:3365–3368.
- Cheung B, Hocker JE, Smith SA, Norris MD, Haber M, Marshall GM: Favorable prognostic significance of high-level retinoic acid receptor beta expression in neuroblastoma mediated by effects on cell cycle regulation. Oncogene 1998;17:751–759.
- Qualman SJ, O’Dorisio MS, Fleshman DJ, Shimada H, O’Dorisio TM: Neuroblastoma. Correlation of neuropeptide expression in tumor tissue with other prognostic factors. Cancer 1992;70:2005–2012.
Kogner P, Bjellerup P, Svensson T, Theodorsson E: Pancreastatin immunoreactivity in favourable childhood neuroblastoma and ganglioneuroma. Eur J Cancer 1995;31A:557–560.
- Kogner P, Borgstrom P, Bjellerup P, Schilling FH, Refai E, Jonsson C, Dominici C, Wassberg E, Bihl H, Jacobsson H, Theodorsson E, Hassan M: Somatostatin in neuroblastoma and ganglioneuroma. Eur J Cancer 1997;33:2084–2089.
- Brodeur GM, Seeger RC, Barrett A, Berthold F, Castleberry RP, D’Angio G, De Bernardi B, Evans AE, Favrot M, Freeman AI, et al: International criteria for diagnosis, staging and response to treatment in patients with neuroblastoma. J Clin Oncol 1988;6:1874–1881.
Sambrook J, Fritsch EF, Maniatis T: Molecular Cloning: A Laboratory Manual, ed 2. New York, Cold Spring Harbor Laboratory Press, 1989.
- Takita J, Hayashi Y, Kohno T, Shiseki M, Yamaguchi N, Hanada R, Yamamoto K, Yokota J: Allelotype of neuroblastoma. Oncogene 1995;11:1829–1834.
- Takita J, Hayashi Y, Yokota J: Loss of heterozygosity in neuroblastomas – an overview. Eur J Cancer 1997;33:1971–1973.
- Nicholl J, Kofler B, Sutherland GR, Shine J, Iismaa TP: Assignment of the gene encoding human galanin receptor (GALNR) to 18q23 by in situ hybridization. Genomics 1995;30:629–630.
- Crawford J, Hort YJ, Shine J, Iismaa TP: Human GALR1 galanin receptor (GALNR). Map position 18q23. Chromosome Res 1999;7:243.
- Iismaa TP, Fathi Z, Hort YJ, Iben LG, Dutton JL, Baker E, Sutherland GR, Shine J: Structural organization and chromosomal localization of three human galanin receptor genes. Ann NY Acad Sci 1998;863:56–63.
- Kropp J, Hofmann M, Bihl H: Comparison of MIBG and pentetreotide scintigraphy in children with neuroblastoma. Is the expression of somatostatin receptors a prognostic factor? Anticancer Res 1997;17:1583–1588.
- Briganti V, Sestini R, Orlando C, Bernini G, La Cava G, Tamburini A, Raggi CC, Serio M, Maggi M: Imaging of somatostain receptors by indium-111-pentetreotide correlates with quantitative determination of somatostatin receptor type 2 gene expression in neuroblastoma tumors. Clin Cancer Res 1997;3:2385–2391.
- Hanauer A, Mandel JL: The glyceraldehyde 3 phosphate dehydrogenase gene family: Structure of a human cDNA and of an X chromosome linked pseudogene; amazing complexity of the gene family in mouse. EMBO J 1984;3:2627–2633.
- McKnight GL, Karlsen AE, Kowalyk S, Mathewes SL, Sheppard PO, O’Hara PJ, Taborsky GJ Jr: Sequence of human galanin and its inhibition of glucose-stimulated insulin secretion from RIN cells. Diabetes 1992;41:82–87.
- Jacoby AS, Webb GC, Liu ML, Kofler B, Hort YJ, Fathi Z, Bottema CDK, Shine J, Iismaa TP: Structural organization of the mouse and human GALR1 galanin receptor genes (Galnr and GALNR) and chromosomal localization of the mouse gene. Genomics 1997;45:496–508.
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