Neuroendocrine Differentiation in Prostate Cancer

  • Renato Franco
  • Paolo Chieffi
  • Sisto Perdonà
  • Gaetano Facchini
  • Michele Caraglia


Neuroendocrine differentiation (ND) is widely observed in prostate cancer (PC). Its role in clinical practice is controversial, but preclinical and clinical evidences underline the association of ND with poor prognosis in PC patients. Neuroendocrine (NE) cells could condition the PC progression, mainly stimulating the PC exocrine neoplastic cells proliferation through the production of paracrine growth factors. Thus, the castrated adapted neoplastic cells are favored to outgrowth through an androgen receptor independent mechanism. Moreover proportion of NE cells in PC increases because of tumor treatment, mainly androgen deprivation therapy, enormously amplifying the promotion of the PC exocrine component growth stimulated by neuroendocrine paracrine growth factors.

This chapter provides an overview of the most relevant clinical studies demonstrating a significant correlation between ND and PC behavior, indicating that ND could represent a prognostic parameter in PC, and strongly suggesting that NE cells in a castrate resistant patients could be targeted through specific treatment.


Prostate Cancer Androgen Receptor Prostate Specific Antigen Androgen Deprivation Therapy Prostate Cancer Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Neuroendocrine differentiation




Prostate cancer


The prostate specific antigen




Neuron-specific enolase


Vasoactive intestinal peptide


Bombesin/gastrin releasing peptide


Alpha-human chorionic gonadotropin


Parathyroid hormonerelated protein


Vascular endothelial growth factor


Small cell carcinomas


Prostatic intraepithelial neoplasia


Alpha-methylacyl-CoA racemase


Androgen deprivation therapy


Urokinase-type plasminogen activator


Plasminogen activator inhibitor-1




Microvascular density


Mitogen activated protein kinases


Cyclic AMP-dependent protein kinase


Phosphatidylinositol 3-kinase


Cyclin-dependent kinase


Chromogranin B


Chromogranin C


Progastrin-releasing peptide


Prostatic hyperplasia


Performance status


Positron emission tomography




Diethylenetriaminepentaacetic acid




Overall survival


Time to progression


1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid


Protein tyrosine phosphatase


  1. Abdul M, Anezinis PE, Logothetis CJ et al (1994) Growth inhibition of human prostatic carcinoma cell lines by serotonin antagonists. Anticancer Res 14:1215–1220PubMedGoogle Scholar
  2. Abrahamsson PA, Wadstrom LB, Alumets J et al (1986) Peptide hormone- and serotonin-immunoreactive cells in normal and hyperplastic prostate glands. Pathol Res Prac 181:675–683Google Scholar
  3. Abrahamsson PA, Wadstrom LB, Alumets J et al (1987) Peptide-hormone and serotonin-immunoreactive tumour cells in carcinoma of the prostate. Pathol Res Pract 182:298–307PubMedGoogle Scholar
  4. Ahlgren G, Pedersen K, Lundberg S et al (2000) Regressive changes and neuroendocrine differentiation in prostate cancer after neoadjuvant hormonal treatment. Prostate 42:274–279PubMedGoogle Scholar
  5. Albrecht M, Doroszewicz J, Gillen S et al (2004) Proliferation of prostate cancer cells and activity of neutral endopeptidase is regulated by bombesin and IL-1beta with IL-1beta acting as a modulator of cellular differentiation. Prostate 58:82–94PubMedGoogle Scholar
  6. Allen FJ, Van Velden DJ, Heyns CF (1995) Are neuroendocrine cells of practical value as an independent prognostic parameter in prostate cancer? Br J Urol 75:751–754PubMedGoogle Scholar
  7. Angelsen A, Syversen U, Stridsberg M et al (1997) Use of neuroendocrine serum markers in the follow-up of patients with cancer of the prostate. Prostate 31:110–117PubMedGoogle Scholar
  8. Aprikian AG, Cordon-Cardo C, Fair WR et al (1993) Characterization of neuroendocrine differentiation in human benign prostate and prostatic adenocarcinoma. Cancer 71:3952–3965PubMedGoogle Scholar
  9. Berruti A, Dogliotti L, Mosca A et al (2000) Circulating neuroendocrine markers in patients with prostate carcinoma. Cancer 88:2590–2597PubMedGoogle Scholar
  10. Berruti A, Mosca A, Tucci M et al (2005) Independent prognostic role of circulating chromogranin a in prostate cancer patients with hormonerefractory disease. Endocr Relat Cancer 12:109–117PubMedGoogle Scholar
  11. Berruti A, Bollito E, Cracco CM et al (2010) The prognostic role of immunohistochemical chromogranin a expression in prostate cancer patients is significantly modified by androgen-deprivation therapy. Prostate 70:718–726PubMedGoogle Scholar
  12. Bonkhoff H (1996) Role of the basal cells in premalignant changes of the human prostate: a stem cell concept for the development of prostate cancer. Eur Urol 30:201–205PubMedGoogle Scholar
  13. Bonkhoff H, Stein U, Remberger K (1994) Multidirectional differentiation in the normal, hyperplastic, and neoplastic human prostate: simultaneous demonstration of cell-specific epithelial markers. Hum Pathol 25:42–46PubMedGoogle Scholar
  14. Bonkhoff H, Stein U, Remberger K (1995) Endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma are postmitotic cells. Hum Pathol 26:167–170PubMedGoogle Scholar
  15. Borre M, Nerstrom B, Overgaard J (2000) 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 6:1882–1890PubMedGoogle Scholar
  16. Bostwick DG, Dousa MK, Crawford BG et al (1994) Neuroendocrine differentiation in prostatic intraepithelial neoplasia and adenocarcinoma. Am J Surg Pathol 18:1240–1246PubMedGoogle Scholar
  17. Bostwick DG, Qian J, Pacelli A et al (2002) Neuroendocrine expression in node positive prostate cancer: correlation with systemic progression and patient survival. J Urol 168:1204–1211PubMedGoogle Scholar
  18. Buchanan G, Greenberg NM, Scher HI et al (2001) Collocation of androgen receptor gene mutations in prostate cancer. Clin Cancer Res 7:1273–1281PubMedGoogle Scholar
  19. Cescato R, Maina T, Nock B et al (2008) Bombesin receptor antagonists may be preferable to agonists for tumor targeting. J Nucl Med 49:318–326PubMedGoogle Scholar
  20. Chevalier S, Defoy I, Lacoste J et al (2002) Vascular endothelial growth factor and signaling in the prostate: more than angiogenesis. Mol Cell Endocrinol 189:169–179PubMedGoogle Scholar
  21. Chung TD, Yu JJ, Kong TA et al (2000) Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines. Prostate 42:1–7PubMedGoogle Scholar
  22. Cohen MK, Arber DA, Coffield KS et al (1994) Neuroendocrine differentiation in prostatic adenocarcinoma and its relationship to tumor progression. Cancer 74:1899–1903PubMedGoogle Scholar
  23. Collado B, Gutierrez-Canas I, Rodriguez-Henche N et al (2004) Vasoactive intestinal peptide increases vascular endothelial growth factor expression and neuroendocrine differentiation in human prostate cancer LNCaP cells. Regul Pept 119:69–75PubMedGoogle Scholar
  24. Collado B, Sanchez MG, Diaz-Laviada I et al (2005) Vasoactive intestinal peptide (VIP) induces c-fos expression in LNCaP prostate cancer cells through a mechanism that involves Ca2+ signalling. Implications in angiogenesis and neuroendocrine differentiation. Biochim Biophys Acta 1744:224–233PubMedGoogle Scholar
  25. Cox ME, Deeble PD, Bissonette EA et al (2000) Activated 3′,5′-cyclic AMP-dependent protein kinase is sufficient to induce neuroendocrinelike differentiation of the LNCaP prostate tumor cell line. J Biol Chem 275:13812–13818PubMedGoogle Scholar
  26. Deeble PD, Murphy DJ, Parsons SJ et al (2001) Interleukin-6-, cyclic AMP-mediated signalling potentiates neuroendocrine differentiation of LNCaP prostate tumor cells. Mol Cell Biol 21:8471–8482PubMedGoogle Scholar
  27. Deftos LJ, Nakada S, Burton DW et al (1996) Immunoassay and immunohistology studies of chromogranin a as a neuroendocrine marker in patients with carcinoma of the prostate. Urology 48:58–62PubMedGoogle Scholar
  28. Deng X, Liu H, Huang J et al (2008) Ionizing radiation induces prostate cancer neuroendocrine differentiation through interplay of CREB and ATF2: implications for disease progression. Cancer Res 68:9663–9670PubMedGoogle Scholar
  29. di Sant’Agnese PA (1992) Neuroendocrine differentiation in carcinoma of the prostate. Diagnostic, prognostic, and therapeutic implications. Cancer 70:254–268PubMedGoogle Scholar
  30. di Sant’Agnese PA (1998) Neuroendocrine differentiation in prostatic carcinoma: an update. Prostate 36(8):74–79Google Scholar
  31. Dizeyi N, Konrad L, Bjartell A et al (2002) Localization and mRNA expression of somatostatin receptor subtypes in human prostatic tissue and prostate cancer cell lines. Urol Oncol 7:91–98PubMedGoogle Scholar
  32. Erasmus CE, Verhagen WI, Wauters CA et al (2002) Brain metastasis from prostate small cell carcinoma: not to be neglected. Can J Neurol Sci 29:375–377PubMedGoogle Scholar
  33. Facchini G, Caraglia M, Morabito A et al (2010) Metronomic administration of zoledronic acid and taxotere combination in castration resistant prostate cancer patients: phase I ZANTE trial. Cancer Biol Ther 10:543–548PubMedGoogle Scholar
  34. Festuccia C, Guerra F, D’Ascenzo S (1998) In vitro regulation of pericellular proteolysis in prostatic tumor cells treated with bombesin. Int J Cancer 75:418–431PubMedGoogle Scholar
  35. Fizazi K, De Bono JS, Flechon A et al (2012) Randomised phase II study of CNTO328 (CNTO 328), an anti-IL-6 monoclonal antibody, in combination with mitoxantrone/prednisone versus mitoxantrone/prednisone alone in metastatic castration-resistant prostate cancer. Eur J Cancer 48:85–93PubMedGoogle Scholar
  36. Ghannoum JE, DeLellis RA, Shin SJ (2004) Primary carcinoid tumor of the prostate with concurrent adenocarcinoma: a case report. Int J Surg Pathol 12:167–170PubMedGoogle Scholar
  37. Grobholz R, Bohrer MH, Siegsmund M et al (2000) Correlation between neovascularisation and neuroendocrine differentiation in prostatic carcinoma. Pathol Res Pract 196(5):277–284PubMedGoogle Scholar
  38. Grobholz R, Griebe M, Sauer CG et al (2005) Influence of neuroendocrine tumor cells on proliferation in prostatic carcinoma. Hum Pathol 36:562–570PubMedGoogle Scholar
  39. Guillemot F, Lo LC, Johnson JE et al (1993) Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons. Cell 75:463–476PubMedGoogle Scholar
  40. Hansson J, Abrahamsson PA (2003) Neuroendocrine differentiation in prostate carcinoma. Scand J Urol Nephrol 37(Suppl 212):28–36Google Scholar
  41. Helpap B (2002) Morphology and therapeutic strategies for neuroendocrine tumors of the genitourinary tract. Cancer 95:1415–1420PubMedGoogle Scholar
  42. Hofmann M, Machtens S, Stief C et al (2004) Feasibility of Ga-68-DOTABOM PET in prostate carcinoma patients [abstract]. J Nucl Med 45:449PGoogle Scholar
  43. Huang J, di Sant’'Agnese P (2002) Neuroendocrine differentiation in prostate cancer: an overview. In: Lamberts S (ed) Advances in oncology: the expanding role of octreotide. Bioscientifica Ltd, Bristol, pp 243–262Google Scholar
  44. Huang J, Yao JL, Zhang L et al (2005) Differential expression of interleukin-8 and its receptors in the neuroendocrine and nonneuroendocrine compartments of prostate cancer. Am J Pathol 166:1807–1815PubMedGoogle Scholar
  45. Huang J, Yao JL, Di Sant’agnese PA et al (2006) Immunohistochemical characterization of neuro-endocrine cells in prostate cancer. Prostate 66:1399–1406PubMedGoogle Scholar
  46. Huss WJ, Gray DR, Werdin ES et al (2004) Evidence of pluripotent human prostate stem cells in a human prostate primary xenograft model. Prostate 60:77–90PubMedGoogle Scholar
  47. Isaacs JT (2008) Prostate stem cells and benign prostatic hyperplasia. Prostate 68:1025–1034PubMedGoogle Scholar
  48. Isaacs JT, Coffey DS (1989) Etiology and disease process of benign prostatic hyperplasia. Prostate Suppl 2:33–50PubMedGoogle Scholar
  49. Ishimaru H, Kageyama Y, Hayashi T et al (2002) Expression of matrix metalloproteinase-9 and bombesin/gastrinreleasing peptide in human prostate cancers and their lymph node metastases. Acta Oncol 41:289–296PubMedGoogle Scholar
  50. Jin RJ, Wang Y, Masumori N et al (2004) NE-10 neuroendocrine cancer promotes the LNCaP xenograft growth in castrated mice. Cancer Res 64:5489–5495PubMedGoogle Scholar
  51. Jin RJ, Lho Y, Connelly L et al (2008) The nuclear factor-kappaB pathway controls the progression of prostate cancer to androgen-independent growth. Cancer Res 68:6762–6769PubMedGoogle Scholar
  52. Jongsma J, Oomen MH, Noordzij MA (2000) Androgen-independent growth is induced by neuropeptides in human prostate cancer cell lines. Prostate 42:34–44PubMedGoogle Scholar
  53. Kadmon D, Thompson TC, Lynch GR et al (1991) Elevated plasma chromogranin-a concentrations in prostatic carcinoma. J Urol 146:358–361PubMedGoogle Scholar
  54. Kamiya N, Suzuki H, Kawamura K et al (2008) Neuroendocrine differentiation in stage D2 prostate cancers. Int J Urol 15:423–428PubMedGoogle Scholar
  55. Kawai S, Hiroshima K, Tsukamoto Y et al (2003) Small cell carcinoma of the prostate expressing prostatespecific antigen and showing syndrome of inappropriate secretion of antidiuretic hormone: an autopsy case report. Pathol Int 53:892–896PubMedGoogle Scholar
  56. Kim J, Adam RM, Freeman MR (2002) Activation of the Erk mitogen-activated protein kinase pathway stimulates neuroendocrine differentiation in LNCaP cells independently of cell cycle withdrawal and STAT3phosphorylation. Cancer Res 62:1549–1554PubMedGoogle Scholar
  57. Kimura N, Hoshi S, Takahaski M et al (1997) Plasma chromogranin a in prostatic carcinoma and neuro-endocrine tumors. J Urol 157:565–568PubMedGoogle Scholar
  58. Kokubo H, Yamada Y, Nishio Y et al (2005) Immunohistochemical study of chromogranin a in stage D2 prostate cancer. Urology 66:135–140PubMedGoogle Scholar
  59. Koutsilieris M, Mitsiades CS, Bogdanos J et al (2004) Combination of somatostatin analog, dexamethasone, and standard androgen ablation therapy in stage D3 prostate cancer patients with bone metastases. Clin Cancer Res 10:4398–4405PubMedGoogle Scholar
  60. Lantry LE, Cappelletti E, Maddalena ME et al (2006) 177Lu-AMBA: synthesis and characterization of a selective 177Lu-labeled GRP receptor agonist for systemic radiotherapy of prostate cancer. J Nucl Med 47:1144–1152PubMedGoogle Scholar
  61. Lee LF, Louie MC, Desai SJ et al (2004) Interleukin-8 confers androgen-independent growth and migration of LNCaP: differential effects of tyrosine kinases Src and FAK. Oncogene 23:2197–2205PubMedGoogle Scholar
  62. Levine L, Lucci JA, Pazdrak B et al (2003) Bombesin stimulates nuclear factor kappa B activation and expression of proangiogenic factors in prostate cancer cells. Cancer Res 63:3495–3502PubMedGoogle Scholar
  63. Liu Y (2008) FDG PET-CT demonstration of metastatic neuroendocrine tumor of prostate. World J Surg Oncol 6:64PubMedGoogle Scholar
  64. Liu IJ, Zafar MB, Lai YH (2001) Fluorodeoxyglucose positron emission tomography studies in diagnosis and staging of clinically organ-confined prostate cancer. Urology 57:108–115PubMedGoogle Scholar
  65. Logothetis C, Hoosein N (1992) The inhibition of the paracrine progression of prostatic cancer as an approach to early therapy of prostatic carcinoma. J Cell Biochem Suppl 16H:128–134PubMedGoogle Scholar
  66. Markwalder R, Reubi JC (1999) Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic transformation. Cancer Res 59:1152–1159PubMedGoogle Scholar
  67. Mazzucchelli R, Lopez-Beltran A, Scarpelli M et al (2002) Predictive factors in prostate needle biopsy. Pathologica 94:331–337PubMedGoogle Scholar
  68. McWilliam LJ, Manson C, George NJ (1997) Neuroendocrine differentiation and prognosis in prostatic adenocarcinoma. Br J Urol 80:287–290PubMedGoogle Scholar
  69. Meyer-Siegler K (2001) COX-2 specific inhibitor, NS-398, increases macrophage migration inhibitory factor expression and induces neuroendocrine differentiation in C4-2b prostate cancer cells. Mol Med 7:850–860PubMedGoogle Scholar
  70. Mitsiades CS, Bogdanos J, Karamanolakis D et al (2006) Randomized controlled clinical trial of a combination of somatostatin analog and dexamethasone plus zoledronate vs. zoledronate in patients with androgen ablation-refractory prostate cancer. Anticancer Res 26:3693–3700PubMedGoogle Scholar
  71. Mori S, Murakami-Mori K, Bonavida B (1999) Interleukin-6 induces G1 arrest through induction of p27(Kip1), a cyclin-dependent kinase inhibitor, and neuron-like morphology in LNCaP prostate tumor cells. Biochem Biophys Res Commun 257:609–614PubMedGoogle Scholar
  72. Mori R, Xiong S, Wang Q et al (2009) Gene profiling and pathway analysis of neuroendocrine transdifferentiated prostate cancer cells. Prostate 69:12–23PubMedGoogle Scholar
  73. Morris MJ, Akhurst T, Larson SM et al (2005) Fluorodeoxyglucose positron emission tomography as an outcome measure for castrate metastatic prostate cancer treated with antimicrotubule chemotherapy. Clin Cancer Res 11:3210–3216PubMedGoogle Scholar
  74. Nagakawa O, Murakami K, Ogasawara M et al (1999) Effect of chromogranin a (pancreastatin) fragment on invasion of prostate cancer cells. Cancer Lett 147:207–213PubMedGoogle Scholar
  75. Nagakawa O, Ogasawara M, Murata J et al (2001) Effect of prostatic neuropeptides on migration of prostate cancer cell lines. Int J Urol 8:65–70PubMedGoogle Scholar
  76. Oyama N, Akino H, Suzuki Y (2001) FDG PET for evaluating the change of glucose metabolism in prostate cancer after androgen ablation. Nucl Med Commun 22:963–968PubMedGoogle Scholar
  77. Palapattu GS, Wu C, Silvers CR et al (2009) Selective expression of CD44, a putative prostate cancer stem cell marker, in neuroendocrine tumor cells of human prostate cancer. Prostate 69:787–798PubMedGoogle Scholar
  78. Pearse AG, Takor T (1979) Embryology of the diffuse neuroendocrine and its relationship to the common peptides. Fed Proc 38:2288–2294PubMedGoogle Scholar
  79. Pinski J, Wang Q, Quek ML et al (2006) Genistein-induced neuroendocrine differentiation of prostate cancer cells. Prostate 66:1136–1143PubMedGoogle Scholar
  80. Powles T, Murray I, Brock C (2007) Molecular position emission tomography and PET/CT imaging in urological malignancies. Eur Urol 51:1511–1521PubMedGoogle Scholar
  81. Reubi JC (2003) Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 24:389–427PubMedGoogle Scholar
  82. Reubi JC, Macke HR, Krenning EP (2005) Candidates for peptide receptor radiotherapy today and in the future. J Nucl Med 46(suppl 1):67S–75SPubMedGoogle Scholar
  83. Rufini V, Calcagni ML, Baum RP (2006) Imaging of neuroendocrine tumors. Semin Nucl Med 36:228–247PubMedGoogle Scholar
  84. Salido M, Vilches J, Lopez A (2000) Neuropeptides bombesin and calcitonin induce resistance to etoposide induced apoptosis in prostate cancer cell lines. Histol Histopathol 15:729–738PubMedGoogle Scholar
  85. Salido M, Vilches J, Roomans GM (2004) Changes in elemental concentrations in LNCaP cells are associated with a protective effect of neuropeptides on etoposide-induced apoptosis. Cell Biol Int 28:397–402PubMedGoogle Scholar
  86. Sarkar D, Singh SK, Mandal AK et al (2010) Plasma chromogranin a: clinical implications in patients with castrate resistant prostate cancer receiving docetaxel chemotherapy. Cancer Biomark 8:81–87PubMedGoogle Scholar
  87. Sauer CG, Roemer A, Grobholz R (2006) Genetic analysis of neuroendocrine tumor cells in prostatic carcinoma. Prostate 66:227–234PubMedGoogle Scholar
  88. Scher HI, Sawyers CL (2005) Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen receptor signaling axis. J Clin Oncol 23:8253–8261PubMedGoogle Scholar
  89. Schmid KW, Helpap B, Totsch M et al (1994) Immunohisto-chemical localization of chromogranin a and B and secretogranin II in normal, hyperplastic and neoplastic prostate. Histopathology 24:233–239PubMedGoogle Scholar
  90. Schoder H, Herrmann K, Gonen M (2005) 2-[18F]fluoro-2-deoxyglucose positron emission tomography for the detection of disease in patients with prostate-specific antigen relapse after radical prostatectomy. Clin Cancer Res 11:4761–4769PubMedGoogle Scholar
  91. Schottelius M, Poethko T, Herz M et al (2004) First 18F-labeled tracer suitable for routine clinical imaging of sst receptor-expressing tumors using positron emission tomography. Clin Cancer Res 10:3593–3606PubMedGoogle Scholar
  92. Schron DS, Gipson T, Mendelsohn G (1984) The histogenesis of small cell carcinoma of the prostate: an immunohistochemical study. Cancer 53:2478–2480PubMedGoogle Scholar
  93. Sciarra A, Monti S, Gentile V et al (2003) Variation in chromogranin. A serum levels during intermittent versus continuous androgen deprivation therapy for prostate adenocarcinoma. Prostate 55:168–179PubMedGoogle Scholar
  94. Seethalakshmi L, Mitra SP, Dobner PR et al (1997) Neurotensin receptor expression in prostate cancer cell line and growth effect of NT at physiological concentrations. Prostate 31:183–192PubMedGoogle Scholar
  95. Segal NH, Cohen RJ, Haffejee Z et al (1994) BCL-2 proto-oncogene expression in prostate cancer and its relationship to the prostatic neuroendocrine cell. Arch Pathol Lab Med 118:616–618PubMedGoogle Scholar
  96. Sehgal I, Thompson TC (1999) Novel regulation of type IV collagenase (matrix metalloproteinase-9 and −2) activities by transforming growth factor-beta1 in human prostate cancer cell lines. Mol Biol Cell 10:407–416PubMedGoogle Scholar
  97. Tanaka M, Suzuki Y, Takaoka K et al (2001) Progression of prostate cancer to neuroendocrine cell tumor. Int J Urol 8:431–436PubMedGoogle Scholar
  98. Tang Y, Wang L, Goloubeva O et al (2009) The relationship of neuroendocrine carcinomas to anti-tumor therapies in TRAMP mice. Prostate 69:1763–1773PubMedGoogle Scholar
  99. Tarle M, Rados N (1991) Investigation on serum neurone-specific enolase in prostatic cancer diagnosis and monitoring: comparative study of a multiple tumor marker assay. Prostate 19:23–33PubMedGoogle Scholar
  100. van Bokhoven A, Varella-Garcia M, Korch C et al (2003) Molecular characterization of human prostate carcinoma cell lines. Prostate 57:205–225PubMedGoogle Scholar
  101. Van de Wiele C, Phonteyne P, Pauwels P et al (2008) Gastrin-releasing peptide receptor imaging in human breast carcinoma versus immunohistochemistry. J Nucl Med 49:260–264PubMedGoogle Scholar
  102. Vilches J, Salido M, Fernandez-Segura E et al (2004) Neuropeptides, apoptosis and ion changes in prostate cancer. Methods of study and recent developments. Histol Histopathol 19:951–961PubMedGoogle Scholar
  103. Waltregny D, Leav I, Signoretti S et al (2001) Androgen-driven prostate epithelial cell proliferation and differentiation in vivo involve the regulation of p27. Mol Endocrinol 15:765–782PubMedGoogle Scholar
  104. Wang Q, Horiatis D, Pinski J (2004) Interleukin-6 inhibits the growth of prostate cancer xenografts in mice by the process of neuroendocrine differentiation. Int J Cancer 111:508–513PubMedGoogle Scholar
  105. Weinstein MH, Partin AW, Veltri RW et al (1996) Neuroendocrine differentiation in prostate cancer: enhanced prediction of progression after radical prostatectomy. Hum Pathol 27:683–687PubMedGoogle Scholar
  106. Wright ME, Tsai MJ, Aebersold R (2003) Androgen receptor represses the neuroendocrine transdifferentiation process in prostate cancer cells. Mol Endocrinol 17:1726–1737PubMedGoogle Scholar
  107. Wu C, Huang J (2007) Phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway is essential for neuroendocrine differentiation of prostate cancer. J Biol Chem 282:3571–3583PubMedGoogle Scholar
  108. Wu G, Burzon DT, di Sant’Agnese PA et al (1996) Calcitonin receptor mRNA expression in the human prostate. Urology 47:376–381PubMedGoogle Scholar
  109. Wu C, Zhang L, Bourne PA et al (2006) Protein tyrosine phosphatase PTP1B is involved in neuroendocrine differentiation of prostate cancer. Prostate 66:1125–1135PubMedGoogle Scholar
  110. Xing N, Qian J, Bostwick D et al (2001) Neuroendocrine cells in human prostate over-express the anti-apoptosis protein survivin. Prostate 48:7–15PubMedGoogle Scholar
  111. Yang JC, Ok JH, Busby JE et al (2009) Aberrant activation of androgen receptor in a new neuropeptide-autocrine model of androgen-insensitive prostate cancer. Cancer Res 69:151–160PubMedGoogle Scholar
  112. Yao JL, Madeb R, Bourne P et al (2006) Small cell carcinoma of the prostate: an immunohistochemical study. Am J Surg Pathol 30:705–712PubMedGoogle Scholar
  113. Yashi M, Nukui A, Kurokawa S et al (2003) Elevated serum progastrin-releasing peptide (31–98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer. Prostate 56:305–312PubMedGoogle Scholar
  114. Yuan TC, Veeramani S, Lin MF (2007) Neuroendocrine-like prostate cancer cells: neuroendocrine transdifferentiation of prostate adenocarcinoma cells. Endocr Relat Cancer 14:531–547PubMedGoogle Scholar
  115. Zhang H, Chen J, Waldherr C et al (2004) Synthesis and evaluation of bombesin derivatives on the basis of pan-bombesin peptides labeled with indium-111, lutetium-177, and yttrium-90 for targeting bombesin receptor-expressing tumors. Cancer Res 64:6707–6715PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Renato Franco
    • 1
  • Paolo Chieffi
    • 2
  • Sisto Perdonà
    • 3
  • Gaetano Facchini
    • 3
  • Michele Caraglia
    • 4
  1. 1.Department of Laboratory MedicineNational Institute of Tumors Fondazione “G. Pascale”NaplesItaly
  2. 2.Department of Experimental MedicinSecond University of NaplesNaplesItaly
  3. 3.Department of Urogynecologic OncologyNational Institute of Tumors Fondazione “G. Pascale”NaplesItaly
  4. 4.Department of Biochemistry and BiophysicsSecond University of NaplesNaplesItaly

Personalised recommendations