Skip to main content

Advertisement

SpringerLink
Log in

Galanin and galanin receptors in human gliomas

  • Regular Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Galanin-like immunoreactivity (GAL-LI) and specific GAL binding sites have been shown to be widely distributed in the central nervous system (CNS) and in CNS tumors. GAL and its receptors have also been shown to be present in glial cells, but to date it is still unknown whether human gliomas produce GAL and express GAL receptors. In this study 20 brain tumors consisting of 15 glioblastomas, 4 meningiomas and 1 gliosarcoma were investigated for the presence of GAL-LI and GAL receptors. Immunofluorescence analysis revealed a dense network of GAL-LI positive cellular processes and cell bodies in 18 of the 20 tumors. In contrast, in vitro 125I-labeled GAL receptor autoradiography showed substantial GAL binding in only 6 glioblastoma tissues. Reverse transcription-PCR analysis detected mRNA of all three known galanin receptors in the tumor tissues, with most tumors expressing multiple receptor subtypes. Pharmacological analysis of tumor membrane homogenates with GAL and the specific GAL receptor GalR2 agonist, AR-M1896, revealed that the GAL receptor GalR1 is most likely the receptor responsible for the observed GAL binding in the glioblastomas. No correlation could be found between GAL-LI, the level of GAL binding and proliferative activity as determined by immunostaining with the cell proliferation marker Ki-67.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1. A–C
Fig. 2.

Similar content being viewed by others

References

  1. 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 75:130–138

    CAS  PubMed  Google Scholar 

  2. Camby I, Salmon I, Danguy A, Pasteels JL, Brotchi J, Martinez J, Kiss R (1996) Influence of gastrin on human astrocytic tumor cell proliferation. J Natl Cancer Inst 88:594–600

    CAS  PubMed  Google Scholar 

  3. Camby I, Salmon I, Oiry C, Galleyrand JC, Nagy N, Danguy A, Brotchi J, Pasteels JL, Martinez J, Kiss R (1996) The influence of gastrin and/or cholecystokinin antagonists on the proliferation of three human astrocytic tumor cell lines. Neuropeptides 30:433–437

    CAS  PubMed  Google Scholar 

  4. Carey DG, Iismaa TP, Ho KY, Rajkovic IA, Kelly J, Kraegen EW, Ferguson J, Inglis AS, Shine J, Chisholm DJ (1993) Potent effects of human galanin in man: growth hormone secretion and vagal blockade. J Clin Endocrinol Metab 77:90–93

    PubMed  Google Scholar 

  5. Cassoni P, Sapino A, Stella A, Fortunati N, Bussolati G (1998) Presence and significance of oxytocin receptors in human neuroblastomas and glial tumors. Int J Cancer 77:695–700

    Article  CAS  PubMed  Google Scholar 

  6. Crawley J (1995) Biological actions of galanin. Regul Pept 59:1-16

    Article  CAS  PubMed  Google Scholar 

  7. Evans HF, Huntley GW, Morrison JH, Shine J (1993) Localisation of mRNA encoding the protein precursor of galanin in the monkey hypothalamus and basal forebrain. J Comp Neurol 328:203–212

    CAS  PubMed  Google Scholar 

  8. Fathi Z, Battaglino PM, Iben LG, Li H, Baker E, Zhang D, McGovern R, Mahle CD, Sutherland GR, Iismaa TP, Dickinson KE, Zimanyi IA (1998) Molecular characterization, pharmacological properties and chromosomal localization of the human GALR2 galanin receptor. Brain Res Mol Brain Res 58:156–169

    PubMed  Google Scholar 

  9. Felix I, Bilbao JM, Asa SL, Tyndel F, Kovacs K, Becker LE (1994) Cerebral and cerebellar gangliocytomas: a morphological study of nine cases. Acta Neuropathol 88:246–251

    CAS  PubMed  Google Scholar 

  10. Habert-Ortoli E, Amiranoff B, Loquet I, Laburthe M, Mayaux JF (1994) Molecular cloning of a functional human galanin receptor. Proc Natl Acad Sci USA 91:9780–9783

    PubMed  Google Scholar 

  11. Heuillet E, Bouaiche Z, Menager J, Dugay P, Munoz N, Dubois H, Amiranoff B, Crespo A, Lavayre J, Blanchard JC, Coole A (1994) The human galanin receptor: ligand-binding and functional characteristics in the Bowes melanoma cell line. Eur J Pharmacol 269:139–147

    Article  CAS  PubMed  Google Scholar 

  12. Hosli E, Ledergerber M, Kofler A, Hosli L (1997) Evidence for the existence of galanin receptors on cultured astrocytes of rat CNS: colocalization with cholinergic receptors. J Chem Neuroanat 13:95–103

    Article  CAS  PubMed  Google Scholar 

  13. Hulting AL, Land T, Berthold M, Langel U, Hokfelt T, Bartfai T (1993) Galanin receptors from human pituitary tumors assayed with human galanin as ligand. Brain Res 625:173–176

    CAS  PubMed  Google Scholar 

  14. Iismaa TP, Shine J (1999) Galanin and galanin receptors. Results Probl Cell Differ 26:257–291

    CAS  PubMed  Google Scholar 

  15. Kolakowski LF Jr, 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 (1998) Molecular characterization and expression of cloned human galanin receptors GALR2 and GALR3. J Neurochem 71:2239–2251

    CAS  PubMed  Google Scholar 

  16. Lang R, Berger A, Hermann A, Kofler B (2001) Biphasic response to human galanin of extracellular acidification in human Bowes melanoma cells. Eur J Pharmacol 423:135–141

    Article  CAS  PubMed  Google Scholar 

  17. Leung B, Iisma TP, Leung KC, Hort YJ, Turner J, Sheehy JP, Ho KK, Lismaa TP (2002) Galanin in human pituitary adenomas: frequency and clinical significance. Clin Endocrinol (Oxf) 56:397–403

    Google Scholar 

  18. Liu HX, Brumovsky P, Schmidt R, Brown W, Payza K, Hodzic L, Pou C, Godbout C, Hokfelt T (2001) Receptor subtype-specific pronociceptive and analgesic actions of galanin in the spinal cord: selective actions via GalR1 and GalR2 receptors. Proc Natl Acad Sci USA 98:9960–9964

    Article  CAS  PubMed  Google Scholar 

  19. Maxwell M, Naber SP, Wolfe HJ, Galanopoulos T, Hedley-Whyte ET, Black PM, Antoniades HN (1990) Coexpression of platelet-derived growth factor (PDGF) and PDGF-receptor genes by primary human astrocytomas may contribute to their development and maintenance. J Clin Invest 86:131–140

    CAS  PubMed  Google Scholar 

  20. Merchenthaler I, Lopez FJ, Negro-Vilar A (1993) Anatomy and physiology of central galanin-containing pathways. Prog Neurobiol 40:711–769

    CAS  PubMed  Google Scholar 

  21. Ohtaki T, Kumano S, Ishibashi Y, Ogi K, Matsui H, Harada M, Kitada C, Kurokawa T, Onda H, Fujino M (1999) Isolation and cDNA cloning of a novel galanin-like peptide (GALP) from porcine hypothalamus. J Biol Chem 274:37041–37045

    CAS  PubMed  Google Scholar 

  22. Piroli GG, Cassataro J, Pietranera L, Grillo CA, Ferrini M, Lux-Lantos V, De Nicola AF (2001) Progestin regulation of galanin and prolactin gene expression in oestrogen-induced pituitary tumours. J Neuroendocrinol 13:302–309

    Article  CAS  PubMed  Google Scholar 

  23. Plate KH, Breier G, Weich HA, Risau W (1992) Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359:845–848

    CAS  PubMed  Google Scholar 

  24. Priller J, Haas CA, Reddington M, Kreutzberg GW (1998) Cultured astrocytes express functional receptors for galanin. Glia 24:323–328

    Article  CAS  PubMed  Google Scholar 

  25. Reubi JC, Lang W, Maurer R, Koper JW, Lamberts SW (1987) Distribution and biochemical characterization of somatostatin receptors in tumors of the human central nervous system. Cancer Res 47:5758–5764

    CAS  PubMed  Google Scholar 

  26. Schlegel U, Moots PL, Rosenblum MK, Thaler HT, Furneaux HM (1990) Expression of transforming growth factor alpha in human gliomas. Oncogene 5:1839–1842

    CAS  PubMed  Google Scholar 

  27. Stockhammer G, Manley GT, Johnson R, Rosenblum MK, Samid D, Lieberman FS (1995) Inhibition of proliferation and induction of differentiation in medulloblastoma- and astrocytoma-derived cell lines with phenylacetate. J Neurosurg 83:672–681

    Google Scholar 

  28. Wiesenhofer B, Stockhammer G, Kostron H, Maier H, Hinterhuber H, Humpel C (2000) Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GFR-alpha 1) are strongly expressed in human gliomas. Acta Neuropathol 99:131–137

    CAS  PubMed  Google Scholar 

  29. Wynick D, Hammond PJ, Akinsanya KO, Bloom SR (1993) Galanin regulates basal and oestrogen-stimulated lactotroph function. Nature 364:529–532

    CAS  PubMed  Google Scholar 

  30. Xu Z, Cortes R, Villar M, Morino P, Castel MN, Hokfelt T (1992) Evidence for upregulation of galanin synthesis in rat glial cells in vivo after colchicine treatment. Neurosci Lett 145:185–188

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Children's Cancer Foundation Salzburg and the "Vereinigung zur Förderung Pädiatrischer Forschung und Fortbildung Salzburg".

Author information

Authors and Affiliations

  1. Department of Pediatrics, General Hospital, Muellner Hauptstrasse 48, 5020, Salzburg, Austria

    Alexandra Berger, Radmila Santic, Wolfgang Sperl & Barbara Kofler

  2. Institute of Pathology, General Hospital, Salzburg, Austria

    Cornelia Hauser-Kronberger

  3. Institute of Neuropathology, Christian-Doppler-Klinik, Salzburg, Austria

    Michael Huemer

  4. Department of Psychiatry and Department of Neurology, University Hospital, Innsbruck, Austria

    Christian Humpel & Günther Stockhammer

Authors
  1. Alexandra Berger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Radmila Santic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dietmar Almer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cornelia Hauser-Kronberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Huemer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christian Humpel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Günther Stockhammer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wolfgang Sperl
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Barbara Kofler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Barbara Kofler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berger, A., Santic, R., Almer, D. et al. Galanin and galanin receptors in human gliomas. Acta Neuropathol 105, 555–560 (2003). https://doi.org/10.1007/s00401-003-0680-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-003-0680-7

Keywords

Search

Navigation