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Expression of endothelin system in neuroblastic tumors: close association of endothelin-1 and endothelin B receptor expression with differentiation of tumor cells

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Abstract

Although a critical role of the endothelin (ET) system in differentiation of neural crest cells has been reported, implication of the ET system in human neuroblastic tumors has not been fully elucidated. We immunohistochemically examined for localization of ET-1, ET-3, ET-A receptor (ET-A), and ET-B receptor (ET-B) in 24 ganglioneuromas, 8 ganglioneuroblastomas, 37 neuroblastomas, 14 normal sympathetic ganglia, and 10 fetal adrenal glands with regard to neuroblastic cell differentiation. Neuroblasts in fetal adrenal glands expressed ET-B (100%) alone. Immature ganglionic cells in sympathetic ganglia of fetus frequently expressed ET-1 (86%) and ET-B (100%), while ET-A was occasionally detected (28%). Ganglionic cells of mature adult ganglia consistently harbored ET-1 (100%) and, infrequently, ET-3 (21%) or ET-B (29%). Expression of ET-1 and ET-B was closely associated with tumor cell differentiation: the expression frequency of ET-1 or ET-B was 16% or 46% in neuroblastomas; 100% or 88% in ganglioneuroblastomas; and 96% or 92% in ganglioneuromas. In contrast, ET-3 and ET-A showed no association with tumor cell differentiation: the expression frequency of ET-3 or ET-A was 26% or 14% in neuroblastomas; 63% or 13% in ganglioneuroblastomas; and 29% or 21% in ganglioneuromas. In conclusion, ET-1 and ET-B are expressed with differentiation of neuroblastic tumors.

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References

  1. Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, Masaki T (1989) The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci U S A 86:2863–2867

    Article  PubMed  CAS  Google Scholar 

  2. Arai H, Hori S, Aramori I, Ohkubo H, Nakanishi S (1990) Cloning and expression of a cDNA encoding an endothelin receptor. Nature (Lond) 348:730–732

    Article  CAS  Google Scholar 

  3. Sakurai T, Yanagisawa M, Takuwa Y, Miyazaki H, Kimura S, Goto K, Masaki T (1990) Cloning of a cDNA encoding a non-isopeptideselective subtype of the endothelin receptor. Nature (Lond) 348:732–735

    Article  CAS  Google Scholar 

  4. Battistini B, Chailler P, D’Orléans-Juste P, Brière N, Sirois P (1993) Growth regulatory properties of endothelins. Peptides 14:385–399

    Article  PubMed  CAS  Google Scholar 

  5. Stiles JD, Ostrow PT, Balos LL, Greenberg SJ, Plunkett R, Grand W, Heffner RR Jr (1997) Correlation of endothelin-1 and transforming growth factor beta 1 with malignancy and vascularity in human gliomas. J Neuropathol Exp Neurol 56:435–439

    Article  PubMed  CAS  Google Scholar 

  6. Adachi M, Hashido K, Trzeciak A, Watanabe T, Furuichi Y, Miyamoto C (1993) Functional domains of human endothelin receptor. J Cardiovasc Pharmacol 22(suppl 8):S121–S124

    Article  PubMed  CAS  Google Scholar 

  7. Brand M, Le Moullec J-M, Corvol P, Gase J-M (1998) Ontogeny of endothelins-1 and -3, their receptors, and endothelin converting enzyme-1 in the early human embryo. J Clin Invest 101:549–559

    Article  PubMed  CAS  Google Scholar 

  8. Baynash AG, Hosoda K, Giaid A, Richardson JA, Emoto N, Hammer RE. Yanagisawa M (1994) Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Cell 79:1277–1285

    Article  PubMed  CAS  Google Scholar 

  9. Takahashi K, Totsune K, Kitamuro T, Sone M, Murakami O, Shibahara S (2002) Three vasoactive peptides, endothelin-1, adrenomedullin and urotensin-II, in human tumour cell lines of different origin: expression and effects on proliferation. Clin Sci 103(suppl 48):35S–38S

    PubMed  CAS  Google Scholar 

  10. Berry PA, Zhang YF, Carter ND, Burchill SA (2001) Decreased wild-type full-length ET-A and ET-B receptors in neuroblastoma and Ewing sarcoma cells. Med Pediatr Oncol 36:142–146

    Article  PubMed  CAS  Google Scholar 

  11. Berry P, Burchill S (2002) Endothelins may modulate invasion and proliferation of Ewing’s sarcoma and neuroblastoma. Clin Sci 103(suppl 48):322S–326S

    PubMed  CAS  Google Scholar 

  12. Watanabe K, Hiraki H, Hasegawa H, Tanigawa T, Emura I, Honma K, Ishikawa H, Fukuda T, Suzuki T (1997) Immunohistochemical localization of endothelin-1, endothelin-3 and endothelin receptors in human pheochromocytoma and paraganglioma. Pathol Int 47:540–546

    Article  PubMed  CAS  Google Scholar 

  13. Lee M-E, dela Monte SM, Ng S-C, Bloch KD, Quertermous T (1991) Expression of the potent vasoconstrictor endothelin in the human central nervous system. J Clin Invest 86:141–147

    Article  Google Scholar 

  14. Giaid A, Gibson SJ, Herrero MT, Gentleman S, Legon S, Yanagisawa M, Masaki T, Ibrahim NB, Roberts GW, Rossi ML (1991) Topographical localization of endothelin mRNA and peptide immunoreactivity in neurons of the human brain. Histochemistry (Oxf) 95:303–314

    CAS  Google Scholar 

  15. Giaid A, Gibson SJ, Ibrahim NBN, Legon S, Bloom SR, Yanagisawa M, Masaki T, Varndell IM, Polak JM (1989) Endothelin 1, an endothelium-derived peptide, is expressed in neurons of the human spinal cord and dorsal root ganglia. Proc Natl Acad Sci U S A 86:7634–7638

    Article  PubMed  CAS  Google Scholar 

  16. Rubanyi GM, Polokoff MA (1994) Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol Rev 46:328–415

    Google Scholar 

  17. Nataf V, Lecoin L, Eichmann A, Le Dourain NM (1996) Endothelin-B receptor is expressed by neural crest cells in the avian embryo. Proc Natl Acad Sci U S A 93:9645–9650

    Article  PubMed  CAS  Google Scholar 

  18. Wilkes LC, Boarder MR (1991) Characterization of the endothelin binding site on bovine adrenomedullary chromaffin cells: comparison with vascular smooth muscle cells. Evidence for receptor heterogeneity. J Pharmacol Exp Ther 256:628–633

    PubMed  CAS  Google Scholar 

  19. Wikes LC, Boarder MR (1991) Characterization of endothelin receptors on a human neuroblastoma cells line: evidence for the ETA subtype. Br J Pharmacol 104:750–754

    Google Scholar 

  20. Yohn JJ, Smith C, Stevens T, Hoffman TA, Morelli JG, Hurt DL, Yanagisawa M, Kane MA, Zamora MR (1994) Human melanoma cells express functional endothelin-1 receptors. Biochem Biophys Res Commun 201:449–457

    Article  PubMed  CAS  Google Scholar 

  21. Kikuchi K, Nakagawa H, Kadono T, Etoh T, Byers HR, Mihm MC, Tamaki K (1996) Decreased ET(B) receptor expression in human metastatic melanoma cells. Biochem Biophys Res Commun 219:734–739

    Article  PubMed  CAS  Google Scholar 

  22. Nelson JB, Chan-Tack K, Hedican SP, Magnuson SR, Opgenorth TJ, Bova GS, Simons JW (1996) Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate cancer. Cancer Res 56:663–668

    PubMed  CAS  Google Scholar 

  23. Hasson PM, Thappa V, Landman MJ, Fanburg BL (1992) Endothelin-1: mitogenic activity on pulmonary artery smooth muscle cells and release from hypoxic endothelial cells. Proc Soc Exp Biol Med 199:165–170

    Google Scholar 

  24. Takagi Y, Fukasa M, Takata KS, Yoshimi H, Tokunaga O, Fujita T (1990) Autocrine effect of endothelin on DNA synthesis in human vascular endothelial cells. Biochem Biophys Res Commun 168:527–543

    Article  Google Scholar 

  25. Yada Y, Higashi K, Imokawa G (1991) Effects of endothelins on signal transduction and proliferation in human melanocytes. J Biol Chem 266:18352–18357

    PubMed  CAS  Google Scholar 

  26. Kusuhara M, Yamaguchi K, Kuranami M, Suzaki A, Ishikawa S, Moon H, Adachi I, Hori S, Handa S (1992) Stimulation of anchorage-independent cell growth by endothelin in NRK49F cells. Cancer Res 52:3011–3014

    PubMed  CAS  Google Scholar 

  27. Bagnato A, Tecce R, Di Castro V, Catt KJ (1997) Activation of mitogenic signaling by endothelin-1 in ovarian carcinoma cells. Cancer Res 57:1306–1311

    PubMed  CAS  Google Scholar 

  28. Lahav R, Ziller C, Dupin E, Le Douran (1996) Endothelin 3 promotes neural crest cell proliferation and mediates a vast increase in melanocyte number in culture. Proc Natl Acad Sci U S A 93:3892–3897

    Article  PubMed  CAS  Google Scholar 

  29. Hoshi N, Hitomi J, Kusakabe T, Fukuda T, Hirota M, Suzuki T (2008) Distinct morphological and immunohistochemical features and different growth rates among four human neuroblastomas heterotransplanted into nude mice. Med Mol Morphol 41: 151–159

    Article  PubMed  CAS  Google Scholar 

  30. Suzuki T, Kikkawa F, Ino K, Nagasaka T, Tamakoshi K, Mizutani S (2001) Imbalance between neutral endopeptidase 24.11 and endothelin-1 expression in human endometrial carcinoma. Oncology 60:258–267

    Article  PubMed  CAS  Google Scholar 

  31. Barnes K, Walkden BJ, Wilkinson TC, Turner AJ (1997) Expression of endothelin-converting enzyme in both neuroblastoma and glial cell lines and its localization in rat hippocampus. J Neurochem 68:570–577

    Article  PubMed  CAS  Google Scholar 

  32. Fisk L, Nalivaeva NN, Turner AJ (2006) Regulation of endothelin-converting enzyme-1 expression in human neuroblastoma cells. Exp Biol Med 231:1048–1053

    CAS  Google Scholar 

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Correspondence to Nobuo Hoshi.

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Hoshi, N., Sugino, T. & Suzuki, T. Expression of endothelin system in neuroblastic tumors: close association of endothelin-1 and endothelin B receptor expression with differentiation of tumor cells. Med Mol Morphol 42, 110–117 (2009). https://doi.org/10.1007/s00795-008-0437-4

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  • DOI: https://doi.org/10.1007/s00795-008-0437-4

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