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Clinical implications of neuroendocrine differentiation in prostate cancer

Prostate Cancer and Prostatic Diseases volume 10, pages 6–14 (2007)Cite this article

Abstract

The cellular signaling pathways of the prostate play a central role in the induction, maintenance, and progression of prostate cancer (CaP). Neuroendocrine (NE) cells demonstrate attributes that suggest they are an integral part of these signaling cascades. We summarize what is known regarding NE cells in CaP focusing on NE cellular transdifferentiation. This significant event in CaP progression appears to be accelerated by androgen deprivation (AD) treatment. We examine biochemical pathways that may impact NE differentiation in a chronological manner focusing on AD therapy (ADT) as a central event in inducing androgen-independent CaP. Our analysis is limited to the common adenocarcinoma pattern of CaP and excludes small-cell and carcinoid prostatic variants. In conclusion, we speculate on the future of treatment and research in this area.

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References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C et al. Cancer statistics, 2006. CA Cancer J Clin 2006; 56: 106–130.

    Article  PubMed  Google Scholar 

  2. Huggins C, Hodges C . Studies on prostate cancer: I. The effect of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941; 1: 293–297.

    CAS  Google Scholar 

  3. Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ et al. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med 1998; 339: 1036–1042.

    CAS  PubMed  Google Scholar 

  4. Krijnen JL, Janssen PJ, Ruizeveld de Winter JA, van Krimpen H, Schroder FH, van der Kwast TH . Do neuroendocrine cells in human prostate cancer express androgen receptor? Histochemistry 1993; 100: 393–398.

    CAS  PubMed  Google Scholar 

  5. Bonkhoff H . Neuroendocrine cells in benign and malignant prostate tissue: morphogenesis, proliferation, and androgen receptor status. Prostate Suppl 1998; 8: 18–22.

    CAS  PubMed  Google Scholar 

  6. Pretl K . Zur Frage der Endokrinie der menschlichen Vorsteherdruse. Virchows Arch A 1944; 312: 392–404.

    Google Scholar 

  7. Abrahamsson PA . Neuroendocrine cells in tumour growth of the prostate. Endocr Relat Cancer 1999; 6: 503–519.

    CAS  PubMed  Google Scholar 

  8. Heasley LE . Autocrine and paracrine signaling through neuropeptide receptors in human cancer. Oncogene 2001; 20: 1563–1569.

    CAS  PubMed  Google Scholar 

  9. Andrew A, Kramer B, Rawdon BB . Gut and pancreatic amine precursor uptake and decarboxylation cells are not neural crest derivatives. Gastroenterology 1983; 84: 429–431.

    CAS  PubMed  Google Scholar 

  10. Tutton PJ, Barkla DH . Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells [review]. Anticancer Res 1987; 7: 1–12.

    CAS  PubMed  Google Scholar 

  11. Bonkhoff H, Stein U, Remberger K . Multidirectional differentiation in the normal, hyperplastic, and neoplastic human prostate: simultaneous demonstration of cell-specific epithelial markers. Hum Pathol 1994; 25: 42–46.

    CAS  PubMed  Google Scholar 

  12. Aumuller G, Leonhardt M, Janssen M, Konrad L, Bjartell A, Abrahamsson PA . Neurogenic origin of human prostate endocrine cells. Urology 1999; 53: 1041–1048.

    CAS  PubMed  Google Scholar 

  13. Luttrell LM, Daaka Y, Lefkowitz RJ . Regulation of tyrosine kinase cascades by G-protein-coupled receptors. Curr Opin Cell Biol 1999; 11: 177–183.

    CAS  PubMed  Google Scholar 

  14. Aprikian AG, Han K, Chevalier S, Bazinet M, Viallet J . Bombesin specifically induces intracellular calcium mobilization via gastrin-releasing peptide receptors in human prostate cancer cells. J Mol Endocrinol 1996; 16: 297–306.

    CAS  PubMed  Google Scholar 

  15. Han K, Viallet J, Chevalier S, Zheng W, Bazinet M, Aprikian AG . Characterization of intracellular calcium mobilization by bombesin-related neuropeptides in PC-3 human prostate cancer cells. Prostate 1997; 31: 53–60.

    CAS  PubMed  Google Scholar 

  16. Seethalakshmi L, Mitra SP, Dobner PR, Menon M, Carraway RE . Neurotensin receptor expression in prostate cancer cell line and growth effect of NT at physiological concentrations. Prostate 1997; 31: 183–192.

    CAS  PubMed  Google Scholar 

  17. Festuccia C, Guerra F, D'Ascenzo S, Giunciuglio D, Albini A, Bologna M . In vitro regulation of pericellular proteolysis in prostatic tumor cells treated with bombesin. Int J Cancer 1998; 75: 418–431.

    CAS  PubMed  Google Scholar 

  18. Nakada SY, di Sant'Agnese PA, Moynes RA, Hiipakka RA, Liao S, Cockett AT et al. The androgen receptor status of neuroendocrine cells in human benign and malignant prostatic tissue. Cancer Res 1993; 53: 1967–1970.

    CAS  PubMed  Google Scholar 

  19. Iwamura M, Hellman J, Cockett AT, Lilja H, Gershagen S . Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen. Urology 1996; 48: 317–325.

    CAS  PubMed  Google Scholar 

  20. Diaz M, Abdul M, Hoosein N . Modulation of neuroendocrine differentiation in prostate cancer by interleukin-1 and -2. Prostate Suppl 1998; 8: 32–36.

    CAS  PubMed  Google Scholar 

  21. Spiotto MT, Chung TD . STAT3 mediates IL-6-induced neuroendocrine differentiation in prostate cancer cells. Prostate 2000; 42: 186–195.

    CAS  PubMed  Google Scholar 

  22. Aprikian AG, Cordon-Cardo C, Fair WR, Reuter VE . Characterization of neuroendocrine differentiation in human benign prostate and prostatic adenocarcinoma. Cancer 1993; 71: 3952–3965.

    CAS  PubMed  Google Scholar 

  23. Cohen RJ, Glezerson G, Haffejee Z . Prostate-specific antigen and prostate-specific acid phosphatase in neuroendocrine cells of prostate cancer. Arch Pathol Lab Med 1992; 116: 65–66.

    CAS  PubMed  Google Scholar 

  24. Vashchenko N, Abrahamsson PA . Neuroendocrine differentiation in prostate cancer: implications for new treatment modalities. Eur Urol 2005; 47: 147–155.

    CAS  PubMed  Google Scholar 

  25. Bang YJ, Pirnia F, Fang WG, Kang WK, Sartor O, Whitesell L et al. Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP. Proc Natl Acad Sci USA 1994; 91: 5330–5334.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Deeble PD, Murphy DJ, Parsons SJ, Cox ME . Interleukin-6- and cyclic AMP-mediated signaling potentiates neuroendocrine differentiation of LNCaP prostate tumor cells. Mol Cell Biol 2001; 21: 8471–8482.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Cox ME, Deeble PD, Lakhani S, Parsons SJ . Acquisition of neuroendocrine characteristics by prostate tumor cells is reversible: implications for prostate cancer progression. Cancer Res 1999; 59: 3821–3830.

    CAS  PubMed  Google Scholar 

  28. Iwamura M, Gershagen S, Lapets O, Moynes R, Abrahamsson PA, Cockett AT et al. Immunohistochemical localization of parathyroid hormone-related protein in prostatic intraepithelial neoplasia. Hum Pathol 1995; 26: 797–801.

    CAS  PubMed  Google Scholar 

  29. Bostwick DG, Dousa MK, Crawford BG, Wollan PC . Neuroendocrine differentiation in prostatic intraepithelial neoplasia and adenocarcinoma. Am J Surg Pathol 1994; 18: 1240–1246.

    CAS  PubMed  Google Scholar 

  30. Abrahamsson PA . Neuroendocrine differentiation in prostatic carcinoma. Prostate 1999; 39: 135–148.

    CAS  PubMed  Google Scholar 

  31. Bonkhoff H, Wernert N, Dhom G, Remberger K . Relation of endocrine-paracrine cells to cell proliferation in normal, hyperplastic, and neoplastic human prostate. Prostate 1991; 19: 91–98.

    CAS  PubMed  Google Scholar 

  32. Bonkhoff H, Stein U, Remberger K . Endocrine–paracrine cell types in the prostate and prostatic adenocarcinoma are postmitotic cells. Hum Pathol 1995; 26: 167–170.

    CAS  PubMed  Google Scholar 

  33. Berruti A, Mosca A, Tucci M, Terrone C, Torta M, Tarabuzzi R et al. Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease. Endocr Relat Cancer 2005; 12: 109–117.

    CAS  PubMed  Google Scholar 

  34. Taplin ME, George DJ, Halabi S, Sanford B, Febbo PG, Hennessy KT et al. Prognostic significance of plasma chromogranin a levels in patients with hormone-refractory prostate cancer treated in Cancer and Leukemia Group B 9480 study. Urology 2005; 66: 386–391.

    PubMed  Google Scholar 

  35. Cabrespine A, Guy L, Gachon F, Cure H, Chollet P, Bay JO . Circulating chromogranin a and hormone refractory prostate cancer chemotherapy. J Urol 2006; 175: 1347–1352.

    CAS  PubMed  Google Scholar 

  36. Kim J, Palmer JL, Finn L, Hodges S, Bowes VV, Deftos L et al. The pattern of serum markers in patients with androgen-independent adenocarcinoma of the prostate. Urol Oncol 2000; 5: 97–103.

    CAS  PubMed  Google Scholar 

  37. Cussenot O, Villette JM, Valeri A, Cariou G, Desgrandchamps F, Cortesse A et al. Plasma neuroendocrine markers in patients with benign prostatic hyperplasia and prostatic carcinoma. J Urol 1996; 155: 1340–1343.

    CAS  PubMed  Google Scholar 

  38. Hoosein N, Abdul M, McCabe R, Gero A, Deftos LJ, Banks M et al. Clinical significance of elevation in neuroendocrine factors and interleukin-6 in metastatic prostate cancer. Urol Oncol 1995; 1: 246–251.

    CAS  PubMed  Google Scholar 

  39. Bologna M, Festuccia C, Muzi P, Biordi L, Ciomei M . Bombesin stimulates growth of human prostatic cancer cells in vitro. Cancer 1989; 63: 1714–1720.

    CAS  PubMed  Google Scholar 

  40. Rozengurt E, Sinnett-Smith J . Early signals underlying the induction of the c-fos and c-myc genes in quiescent fibroblasts: studies with bombesin and other growth factors. Prog Nucleic Acid Res Mol Biol 1988; 35: 261–295.

    CAS  PubMed  Google Scholar 

  41. Markwalder R, Reubi JC . Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic transformation. Cancer Res 1999; 59: 1152–1159.

    CAS  PubMed  Google Scholar 

  42. Hoosein NM, Logothetis CJ, Chung LW . Differential effects of peptide hormones bombesin, vasoactive intestinal polypeptide and somatostatin analog RC-160 on the invasive capacity of human prostatic carcinoma cells. J Urol 1993; 149: 1209–1213.

    CAS  PubMed  Google Scholar 

  43. Julius D, Livelli TJ, Jessell TM, Axel R . Ectopic expression of the serotonin 1c receptor and the triggering of malignant transformation. Science 1989; 244: 1057–1062.

    CAS  PubMed  Google Scholar 

  44. Dizeyi N, Bjartell A, Nilsson E, Hansson J, Gadaleanu V, Cross N et al. Expression of serotonin receptors and role of serotonin in human prostate cancer tissue and cell lines. Prostate 2004; 59: 328–336.

    CAS  PubMed  Google Scholar 

  45. Iwamura M, Wu G, Abrahamsson PA, di Sant'Agnese PA, Cockett AT, Deftos LJ . Parathyroid hormone-related protein is expressed by prostatic neuroendocrine cells. Urology 1994; 43: 667–674.

    CAS  PubMed  Google Scholar 

  46. Grobholz R, Bohrer MH, Siegsmund M, Junemann KP, Bleyl U, Woenckhaus M . Correlation between neovascularisation and neuroendocrine differentiation in prostatic carcinoma. Pathol Res Pract 2000; 196: 277–284.

    CAS  PubMed  Google Scholar 

  47. Harper ME, Glynne-Jones E, Goddard L, Thurston VJ, Griffiths K . Vascular endothelial growth factor (VEGF) expression in prostatic tumours and its relationship to neuroendocrine cells. Br J Cancer 1996; 74: 910–916.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Borre M, Nerstrom B, Overgaard J . Association between immunohistochemical expression of vascular endothelial growth factor (VEGF), VEGF-expressing neuroendocrine-differentiated tumor cells, and outcome in prostate cancer patients subjected to watchful waiting. Clin Cancer Res 2000; 6: 1882–1890.

    CAS  PubMed  Google Scholar 

  49. Busby JE, Shih SJ, Yang JC, Kung HJ, Evans CP . Angiogenesis is not mediated by prostate cancer neuropeptides. Angiogenesis 2003; 6: 289–293.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  51. Prenzel N, Zwick E, Daub H, Leserer M, Abraham R, Wallasch C et al. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature 1999; 402: 884–888.

    CAS  PubMed  Google Scholar 

  52. Levine L, Lucci III JA, Pazdrak B, Cheng JZ, Guo YS, Townsend Jr CM et al. Bombesin stimulates nuclear factor kappa B activation and expression of proangiogenic factors in prostate cancer cells. Cancer Res 2003; 63: 3495–3502.

    CAS  PubMed  Google Scholar 

  53. Sherwood ER, Lee C . Epidermal growth factor-related peptides and the epidermal growth factor receptor in normal and malignant prostate. World J Urol 1995; 13: 290–296.

    CAS  PubMed  Google Scholar 

  54. Abrahamsson PA, Anderson J, Boccon-Gibod L, Schulman C, Studer UE, Wirth M . Risks and benefits of hormonal manipulation as monotherapy or adjuvant treatment in localised prostate cancer. Eur Urol 2005; 48: 900–905.

    PubMed  Google Scholar 

  55. Brevini TA, Bianchi R, Motta M . Direct inhibitory effect of somatostatin on the growth of the human prostatic cancer cell line LNCaP: possible mechanism of action. J Clin Endocrinol Metab 1993; 77: 626–631.

    CAS  PubMed  Google Scholar 

  56. Hansson J, Abrahamsson PA . Neuroendocrine pathogenesis in adenocarcinoma of the prostate. Ann Oncol 2001; 12 (Suppl 2): S145–S152.

    PubMed  Google Scholar 

  57. Colao A, Marzullo P, Ferone D, Spiezia S, Cerbone G, Marino V et al. Prostatic hyperplasia: an unknown feature of acromegaly. J Clin Endocrinol Metab 1998; 83: 775–779.

    CAS  PubMed  Google Scholar 

  58. Jongsma J, Oomen MH, Noordzij MA, Van Weerden WM, Martens GJ, van der Kwast TH et al. Androgen deprivation of the PC-310 (correction of prohormone convertase-310) human prostate cancer model system induces neuroendocrine differentiation. Cancer Res 2000; 60: 741–748.

    CAS  PubMed  Google Scholar 

  59. Lee LF, Louie MC, Desai SJ, Yang J, Chen HW, Evans CP et al. Interleukin-8 confers androgen-independent growth and migration of LNCaP: differential effects of tyrosine kinases Src and FAK. Oncogene 2004; 23: 2197–2205.

    CAS  PubMed  Google Scholar 

  60. Lee LF, Guan J, Qiu Y, Kung HJ . Neuropeptide-induced androgen independence in prostate cancer cells: roles of nonreceptor tyrosine kinases Etk/Bmx, Src, and focal adhesion kinase. Mol Cell Biol 2001; 21: 8385–8397.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Huss WJ, Gregory CW, Smith GJ . Neuroendocrine cell differentiation in the CWR22 human prostate cancer xenograft: association with tumor cell proliferation prior to recurrence. Prostate 2004; 60: 91–97.

    PubMed  Google Scholar 

  62. Monti S, Sciarra A, Falasca P, Di Silverio F . Serum concentrations and prostatic gene expression of chromogranin A and PSA in patients affected by prostate cancer and benign prostatic hyperplasia. J Endocrinol Invest 2000; 23: 53.

    Google Scholar 

  63. Ahlgren G, Pedersen K, Lundberg S, Aus G, Hugosson J, Abrahamsson PA . Regressive changes and neuroendocrine differentiation in prostate cancer after neoadjuvant hormonal treatment. Prostate 2000; 42: 274–279.

    CAS  PubMed  Google Scholar 

  64. Feldman BJ, Feldman D . The development of androgen-independent prostate cancer. Nat Rev Cancer 2001; 1: 34–45.

    CAS  PubMed  Google Scholar 

  65. Ueda T, Bruchovsky N, Sadar MD . Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways. J Biol Chem 2002; 277: 7076–7085.

    CAS  PubMed  Google Scholar 

  66. Jongsma J, Oomen MH, Noordzij MA, Romijn JC, van Der Kwast TH, Schroder FH et al. Androgen-independent growth is induced by neuropeptides in human prostate cancer cell lines. Prostate 2000; 42: 34–44.

    CAS  PubMed  Google Scholar 

  67. Culig Z, Hobisch A, Cronauer MV, Radmayr C, Hittmair A, Zhang J et al. Regulation of prostatic growth and function by peptide growth factors. Prostate 1996; 28: 392–405.

    CAS  PubMed  Google Scholar 

  68. Hampel OZ, Kattan MW, Yang G, Haidacher SJ, Saleh GY, Thompson TC et al. Quantitative immunohistochemical analysis of insulin-like growth factor binding protein-3 in human prostatic adenocarcinoma: a prognostic study. J Urol 1998; 159: 2220–2225.

    CAS  PubMed  Google Scholar 

  69. Gregory CW, Kim D, Ye P, D'Ercole AJ, Pretlow TG, Mohler JL et al. Androgen receptor up-regulates insulin-like growth factor binding protein-5 (IGFBP-5) expression in a human prostate cancer xenograft. Endocrinology 1999; 140: 2372–2381.

    CAS  PubMed  Google Scholar 

  70. McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LW, Hsieh JT et al. Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res 1992; 52: 6940–6944.

    CAS  PubMed  Google Scholar 

  71. Furuya Y, Krajewski S, Epstein JI, Reed JC, Isaacs JT . Expression of bcl-2 and the progression of human and rodent prostatic cancers. Clin Cancer Res 1996; 2: 389–398.

    CAS  PubMed  Google Scholar 

  72. Liu AY, Corey E, Bladou F, Lange PH, Vessella RL . Prostatic cell lineage markers: emergence of BCL2+ cells of human prostate cancer xenograft LuCaP 23 following castration. Int J Cancer 1996; 65: 85–89.

    CAS  PubMed  Google Scholar 

  73. Ambrosini G, Adida C, Altieri DC . A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997; 3: 917–921.

    CAS  PubMed  Google Scholar 

  74. Xing N, Qian J, Bostwick D, Bergstralh E, Young CY . Neuroendocrine cells in human prostate over-express the anti-apoptosis protein survivin. Prostate 2001; 48: 7–15.

    CAS  PubMed  Google Scholar 

  75. Sumitomo M, Milowsky MI, Shen R, Navarro D, Dai J, Asano T et al. Neutral endopeptidase inhibits neuropeptide-mediated transactivation of the insulin-like growth factor receptor-Akt cell survival pathway. Cancer Res 2001; 61: 3294–3298.

    CAS  PubMed  Google Scholar 

  76. McMenamin ME, Soung P, Perera S, Kaplan I, Loda M, Sellers WR . Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res 1999; 59: 4291–4296.

    CAS  PubMed  Google Scholar 

  77. Hansson J, Abrahamsson PA . Neuroendocrine differentiation in prostatic carcinoma. Scand J Urol Nephrol Suppl 2003; 212: 28–36.

    Google Scholar 

  78. Aprikian AG, Tremblay L, Han K, Chevalier S . Bombesin stimulates the motility of human prostate-carcinoma cells through tyrosine phosphorylation of focal adhesion kinase and of integrin-associated proteins. Int J Cancer 1997; 72: 498–504.

    CAS  PubMed  Google Scholar 

  79. Bartholdi MF, Wu JM, Pu H, Troncoso P, Eden PA, Feldman RI . In situ hybridization for gastrin-releasing peptide receptor (GRP receptor) expression in prostatic carcinoma. Int J Cancer 1998; 79: 82–90.

    CAS  PubMed  Google Scholar 

  80. Krijnen JL, Bogdanowicz JF, Seldenrijk CA, Mulder PG, van der Kwast TH . The prognostic value of neuroendocrine differentiation in adenocarcinoma of the prostate in relation to progression of disease after endocrine therapy. J Urol 1997; 158: 171–174.

    CAS  PubMed  Google Scholar 

  81. Sciarra A, Di Silverio F . Effect of nonsteroidal antiandrogen monotherapy versus castration therapy on neuroendocrine differentiation in prostate carcinoma. Urology 2004; 63: 523–527.

    PubMed  Google Scholar 

  82. Sciarra A, Monti S, Gentile V, Mariotti G, Cardi A, Voria G et al. Variation in chromogranin A serum levels during intermittent versus continuous androgen deprivation therapy for prostate adenocarcinoma. Prostate 2003; 55: 168–179.

    PubMed  Google Scholar 

  83. Stangelberger A, Schally AV, Varga JL, Zarandi M, Cai RZ, Baker B et al. Inhibition of human androgen-independent PC-3 and DU-145 prostate cancers by antagonists of bombesin and growth hormone releasing hormone is linked to PKC, MAPK and c-jun intracellular signalling. Eur J Cancer 2005; 41: 2735–2744.

    CAS  PubMed  Google Scholar 

  84. Abdul M, Anezinis PE, Logothetis CJ, Hoosein NM . Growth inhibition of human prostatic carcinoma cell lines by serotonin antagonists. Anticancer Res 1994; 14: 1215–1220.

    CAS  PubMed  Google Scholar 

  85. Abdul M, Logothetis CJ, Hoosein NM . Growth-inhibitory effects of serotonin uptake inhibitors on human prostate carcinoma cell lines. J Urol 1995; 154: 247–250.

    CAS  PubMed  Google Scholar 

  86. Hejna M, Schmidinger M, Raderer M . The clinical role of somatostatin analogues as antineoplastic agents: much ado about nothing? Ann Oncol 2002; 13: 653–668.

    CAS  PubMed  Google Scholar 

  87. Sciarra A, Bosman C, Monti G, Gentile V, Gomez AM, Ciccariello M et al. Somatostatin analogues and estrogens in the treatment of androgen ablation refractory prostate adenocarcinoma. J Urol 2004; 172: 1775–1783.

    CAS  PubMed  Google Scholar 

  88. Kaur M, Reed E, Sartor O, Dahut W, Figg WD . Suramin's development: what did we learn? Invest New Drugs 2002; 20: 209–219.

    CAS  PubMed  Google Scholar 

  89. Plonowski A, Schally AV, Varga JL, Rekasi Z, Hebert F, Halmos G et al. Potentiation of the inhibitory effect of growth hormone-releasing hormone antagonists on PC-3 human prostate cancer by bombesin antagonists indicative of interference with both IGF and EGF pathways. Prostate 2000; 44: 172–180.

    CAS  PubMed  Google Scholar 

  90. Sciarra A, Cardi A, Dattilo C, Mariotti G, Di Monaco F, Di Silverio F . New perspective in the management of neuroendocrine differentiation in prostate adenocarcinoma. Int J Clin Pract 2006; 60: 462–470.

    CAS  PubMed  Google Scholar 

  91. Robertson CN, Roberson KM, Padilla GM, O'Brien ET, Cook JM, Kim CS et al. Induction of apoptosis by diethylstilbestrol in hormone-insensitive prostate cancer cells. J Natl Cancer Inst 1996; 88: 908–917.

    CAS  PubMed  Google Scholar 

  92. Angelsen A, Syversen U, Haugen OA, Stridsberg M, Mjolnerod OK, Waldum HL . Neuroendocrine differentiation in carcinomas of the prostate: do neuroendocrine serum markers reflect immunohistochemical findings? Prostate 1997; 30: 1–6.

    CAS  PubMed  Google Scholar 

  93. di Sant'Agnese PA . Neuroendocrine differentiation in carcinoma of the prostate. Diagnostic, prognostic, and therapeutic implications. Cancer 1992; 70: 254–268.

    CAS  PubMed  Google Scholar 

  94. Yashi M, Nukui A, Kurokawa S, Ochi M, Ishikawa S, Goto K et al. Elevated serum progastrin-releasing peptide (31–98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer. Prostate 2003; 56: 305–312.

    CAS  PubMed  Google Scholar 

  95. Salido M, Vilches J, Lopez A, Roomans GM . Neuropeptides bombesin and calcitonin inhibit apoptosis-related elemental changes in prostate carcinoma cell lines. Cancer 2002; 94: 368–377.

    CAS  PubMed  Google Scholar 

  96. Zukowska-Grojec Z, Karwatowska-Prokopczuk E, Fisher TA, Ji H . Mechanisms of vascular growth-promoting effects of neuropeptide Y: role of its inducible receptors. Regul Pept 1998; 75-76: 231–238.

    CAS  PubMed  Google Scholar 

  97. Martinez A, Zudaire E, Portal-Nunez S, Guedez L, Libutti SK, Stetler-Stevenson WG et al. Proadrenomedullin NH2-terminal 20 peptide is a potent angiogenic factor, and its inhibition results in reduction of tumor growth. Cancer Res 2004; 64: 6489–6494.

    CAS  PubMed  Google Scholar 

  98. Ohinata K, Inui A, Asakawa A, Wada K, Wada E, Yoshikawa M . Proadrenomedullin N-terminal 20 peptide (PAMP) elevates blood glucose levels via bombesin receptor in mice. FEBS Lett 2000; 473: 207–211.

    CAS  PubMed  Google Scholar 

  99. Dizeyi N, Bjartell A, Hedlund P, Tasken KA, Gadaleanu V, Abrahamsson PA . Expression of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of their antagonists on prostate cancer cell lines. Eur Urol 2005; 47: 895–900.

    CAS  PubMed  Google Scholar 

  100. Chevalier S, Defoy I, Lacoste J, Hamel L, Guy L, Begin LR et al. Vascular endothelial growth factor and signaling in the prostate: more than angiogenesis. Mol Cell Endocrinol 2002; 189: 169–179.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported in part by NIH Grant KO8 DK60748-01 and Department of Defense Grant PC040161. Mention of trade name, proprietary product or specific equipment does not constitute a guaranty of warranty by the Department of Defense, nor does it imply approval to the exclusion of other products. The views expressed herein represent those of the authors and do not necessarily represent the position of the Department of Defense.

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  1. Department of Urology, Davis Medical Center, University of California at Davis, Sacramento, CA, USA

    E C Nelson, A J Cambio, J C Yang, J-H Ok, P N Lara Jr & C P Evans

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Nelson, E., Cambio, A., Yang, J. et al. Clinical implications of neuroendocrine differentiation in prostate cancer. Prostate Cancer Prostatic Dis 10, 6–14 (2007). https://doi.org/10.1038/sj.pcan.4500922

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