Top

Published in:

01-09-2013 | Laboratory Investigation

Expression of alarin in ependymoma and choroid plexus tumors

Authors: Nicole Eberhard, Serge Weis, Herbert Reitsamer, Barbara Kofler

Published in: Journal of Neuro-Oncology | Issue 2/2013

Abstract

Alarin, a 25 amino acid splice variant of the galanin-like peptide, was originally discovered in gangliocytes of neuroblastic tumors and shown to be expressed in ganglioneuroblastoma and ganglioneuroma but not in undifferentiated neuroblastoma. Recently, in vivo studies have elucidated the physiological functions of alarin in the central nervous system (CNS). Alarin was shown to stimulate food intake, increase body weight, induce luteinizing hormone secretion and stimulate fos-expression in rats; the anatomical localization for these functions correlates well with the varied distribution of the alarin peptide in the brain. Because alarin was originally detected in neuroblastic tumors and is present in a wide range of nuclei in the CNS, we determined in the present study the expression of alarin in a variety of CNS tumors. Immunohistochemical analysis of 179 tumor samples resulted in different alarin-like immunoreactivity (alarin-LI) intensities, which were score-rated from 0 (no alarin stainin), 1 (low intensity), 2 (medium intensity) to 3 (high intensity). Immunohistochemical analyses revealed score 2 or 3 alarin-LI in all choroid plexus tumors (100 %, 7/7) and in the majority of ependymomas (90 %, 52/58), but only in a minority of astrocytomas (15 %, 5/33), meningiomas (14 %, 7/49) and tumors of the cranial nerves (7 %, 1/15). In oligodendrogliomas (0 %, 0/12) and oligoastrocytoma (0 %, 0/5) alarin-LI was not detectable. The high specificity (83 %) of alarin-LI suggests that it might be used as a diagnostic marker for ependymoma in differentiating them from other gliomas such as astrocytomas and oligodendrogliomas.

Alomar SA (2010) Clinical manifestation of central nervous system tumor. Semin Diagn Pathol 27(2):97–104PubMedCrossRef

Barbagallo GM, Caltabiano R, Parisi G, Albanese V, Lanzafame S (2009) Giant cell ependymoma of the cervical spinal cord: case report and review of the literature. Eur Spine J 18(Suppl 2):186–190PubMedCrossRef

Berger A, Santic R, Almer D, Hauser-Kronberger C, Huemer M, Humpel C, Stockhammer G, Sperl W, Kofler B (2003) Galanin and galanin receptors in human gliomas. Acta Neuropathol 105(6):555–560PubMed

Berger A, Santic R, Hauser-Kronberger C, Schilling FH, Kogner P, Ratschek M, Gamper A, Jones N, Sperl W, Kofler B (2005) Galanin and galanin receptors in human cancers. Neuropeptides 39(3):353–359PubMedCrossRef

Berger A, Tuechler C, Almer D, Kogner P, Ratschek M, Kerbl R, Iismaa TP, Jones N, Sperl W, Kofler B (2002) Elevated expression of galanin receptors in childhood neuroblastic tumors. Neuroendocrinology 75(2):130–138PubMedCrossRef

Bollo RJ, Zagzag D, Samadani U (2010) Synchronous choroid plexus papilloma of the fourth ventricle and ependymoma of the filum terminale: case report. Neurosurgery 67(5):E1454–E1459PubMedCrossRef

Boughton CK, Patterson M, Bewick GA, Tadross JA, Gardiner JV, Beale KE, Chaudery F, Hunter G, Busbridge M, Leavy EM, Ghatei MA, Bloom SR, Murphy KG (2010) Alarin stimulates food intake and gonadotrophin release in male rats. Br J Pharmacol 161(3):601–613PubMedCrossRef

Chao MM, Packer RJ, Myseros JS, Rood BR (2011) Isolated extracranial recurrence of anaplastic ependymoma. Pediatr Blood Cancer 56(2):317–318PubMedCrossRef

Dulai MS, Caccamo DV, Briley AL, Edwards MS, Fisher PG, Lehman NL (2010) Intramedullary papillary ependymoma with choroid plexus differentiation and cerebrospinal fluid dissemination to the brain. J Neurosurg Pediatr 5(5):511–517PubMedCrossRef

10.

Eberhard N, Mayer C, Santic R, Navio RP, Wagner A, Bauer HC, Sperk G, Boehm U, Kofler B (2012) Distribution of alarin immunoreactivity in the mouse brain. J Mol Neurosci 46(1):18–32PubMedCrossRef

11.

Fraley GS, Leathley E, Lundy N, Chheng E, King I, Kofler B (2012) Effects of alarin on food intake, body weight and luteinizing hormone secretion in male mice. Neuropeptides 46(2):99–104PubMedCrossRef

12.

Fraley GS, Leathley E, Nickols A, Gerometta E, Coombs E, Colton S, Gallemore S, Lindberg A, Kofler B (2013) Alarin 6–25Cys antagonizes alarin-specific effects on food intake and luteinizing hormone secretion. Neuropeptides 47(1):37–41PubMedCrossRef

13.

Gilbert MR, Ruda R, Soffietti R (2010) Ependymomas in adults. Curr Neurol Neurosci Rep 10(3):240–247PubMedCrossRef

14.

Gladson CL, Prayson RA, Liu WM (2010) The pathobiology of glioma tumors. Annu Rev Pathol 5:33–50PubMedCrossRef

15.

Godfraind C (2009) Classification and controversies in pathology of ependymomas. Childs Nerv Syst 25(10):1185–1193PubMedCrossRef

16.

Klas J, Wolburg H, Terasaki T, Fricker G, Reichel V (2010) Characterization of immortalized choroid plexus epithelial cell lines for studies of transport processes across the blood-cerebrospinal fluid barrier. Cerebrospinal Fluid Res 7:11PubMedCrossRef

17.

Lang R, Gundlach AL, Kofler B (2007) The galanin peptide family: receptor pharmacology, pleiotropic biological actions, and implications in health and disease. Pharmacol Ther 115(2):177–207PubMedCrossRef

18.

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) THe 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 14(2):97–109CrossRef

19.

Poppleton H, Gilbertson RJ (2007) Stem cells of ependymoma. Br J Cancer 96(1):6–10PubMedCrossRef

20.

Rauch I, Kofler B (2010) The galanin system in cancer. EXS 102:223–241PubMed

21.

Rickert CH, Paulus W (2001) Tumors of the choroid plexus. Microsc Res Tech 52(1):104–111PubMedCrossRef

22.

Ruda R, Gilbert M, Soffietti R (2008) Ependymomas of the adult: molecular biology and treatment. Curr Opin Neurol 21(6):754–761PubMedCrossRef

23.

Santic R, Fenninger K, Graf K, Schneider R, Hauser-Kronberger C, Schilling FH, Kogner P, Ratschek M, Jones N, Sperl W, Kofler B (2006) Gangliocytes in neuroblastic tumors express alarin, a novel peptide derived by differential splicing of the galanin-like peptide gene. J Mol Neurosci 29(2):145–152PubMedCrossRef

24.

Santic R, Schmidhuber SM, Lang R, Rauch I, Voglas E, Eberhard N, Bauer JW, Brain SD, Kofler B (2007) Alarin is a vasoactive peptide. Proc Natl Acad Sci USA 104(24):10217–10222PubMedCrossRef

25.

Segal MB (2000) The choroid plexuses and the barriers between the blood and the cerebrospinal fluid. Cell Mol Neurobiol 20(2):183–196PubMedCrossRef

26.

Van Der Kolk N, Madison FN, Mohr M, Eberhard N, Kofler B, Fraley GS (2010) Alarin stimulates food intake in male rats and LH secretion in castrated male rats. Neuropeptides 44(4):333–340CrossRef

27.

Wolburg H, Paulus W (2010) Choroid plexus: biology and pathology. Acta Neuropathol 119(1):75–88PubMedCrossRef

Title: Expression of alarin in ependymoma and choroid plexus tumors
Authors: Nicole Eberhard
Serge Weis
Herbert Reitsamer
Barbara Kofler
Publication date: 01-09-2013
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2013
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-013-1177-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Expression of alarin in ependymoma and choroid plexus tumors

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2013

Systemic treatment after whole-brain radiotherapy may improve survival in RPA class II/III breast cancer patients with brain metastasis

Breast cancer and leptomeningeal disease (LMD): hormone receptor status influences time to development of LMD and survival from LMD diagnosis

CyberKnife radiosurgery for the management of skull base and spinal chondrosarcomas

Outcome comparison between younger and older patients undergoing intracranial meningioma resections

A panel of four cytokines predicts the prognosis of patients with malignant gliomas

Bevacizumab use in disseminated choroid plexus papilloma