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 OJU  Vol.2 No.3 A , October 2012
Neuroendocrine Differentiation in the Progression of Prostate Cancer: An Update on Recent Developments
Abstract: Neuroendocrine (NE) differentiation, either benign or malignant, is the hallmark of prostate cancer (PCa). Clusters of malignant NE cells are found in most prostate cancer cases. NE differentiation is among the non-mutually exclusive theories proposed to explain the progression to androgen independence of PCa. NE differentiation is usually associated with an increased aggressivity and invasiveness of prostate tumors and a poor prognosis. This review aims to present an overview of current knowledge on neuroendocrine differentiation in PCa to improve our understanding of tumour progression and androgen independence. The NE component represents an important therapeutic axis. Development of new generation of drugs that selectively target NE-like cells may lead to the development of new therapeutic modalities for advanced and hormone-refractory PCa.
Cite this paper: V. Perrot, "Neuroendocrine Differentiation in the Progression of Prostate Cancer: An Update on Recent Developments," Open Journal of Urology, Vol. 2 No. 3, 2012, pp. 173-182. doi: 10.4236/oju.2012.223032.
References

[1]   W. A. Schulz, M. Burchardt and M. V. Cronauer, “Molecular Biology of Prostate Cancer,” Molecular Human Reproduction, Vol. 9, 2003, pp. 437-448.

[2]   D. E. Neal, H. Y. Leung, P. H. Powell, F. C. Hamdy and J. L. Donovan, “Unanswered Questions in Screening for Prostate Cancer,” European Journal of Cancer, Vol. 36, No. 10, 2000, pp. 1316-1321.

[3]   A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu and M. J. Thun, “Cancer Statistics, 2009,” CA: A Cancer Journal for Clinicians, Vol. 59, No 4, 2009, pp. 225-249.

[4]   S. P. Balk, “Androgen Receptor as a Target in Androgen-Independent Prostate Cancer,” Urology, Vol. 60, 2002, pp. 132-139.

[5]   H. Bonkhoff, U. Stein and K. Remberger, “Endocrine-Paracrine Cell Types in the Prostate and Prostatic Adenocarcinoma Are Postmitotic Cells,” Human Pathology, Vol. 26, 1995, pp. 167-170.

[6]   P. A. di Sant’Agnese, “Neuroendocrine Cells of the Prostate and Neuroendocrine Differentiation in Prostatic Carcinoma: A Review of Morphologic Aspects,” Urology, Vol. 51, 1998, pp. 121-124.

[7]   H. Bonkhoff, U. Stein and K. Remberger, “Androgen Receptor Status in Endocrine-Paracrine Cell Types of the Normal, Hyperplasia, and Neoplastic Human Prostate,” Virchows Archiv A: Pathological Anatomy and Histology, Vol. 423, 1993, pp. 291-294.

[8]   J. L. M. Krijnen, P. J. A. Janssen, J. A. de Winter Ruizevel, H. Van Krimpen, F. H. Schr?der and T. H. Van der Kwast, “Do Neuroendocrine Cells in Human Prostate Cancer Express Androgen Receptor?” Histochemistry, Vol. 100, 1993, pp. 393-398.

[9]   S. Y. Nakada, P. A. di Sant’Agnese, R. A. Moynes, R. A. Hiipakka, S. Liao, A. T. Cockett and P. A. Abrahamsson, “The Androgen Receptor Status of neuroendocrine Cells in Human Benign and Malignant Prostatic Tissue,” Cancer Research, Vol. 53, 1993, pp. 1967-1970.

[10]   H. Bonkhoff and K. Remberger, “Differentiation Pathways and Histogenic Aspects of Normal and Abnormal Prostatic Growth: A Stem Cell Model,” Prostate, Vol. 28, 1996, pp. 98-106.

[11]   G. Aumuller, M. Leonhardt, M. Janssen, L. Konrad, A. Bjartell and P. A. Abrahamsson, “Neurogenic Origin of Human Prostate Endocrine Cells,” Urology, Vol. 53, 1999, pp. 1041-1048.

[12]   P. A. di Sant’Agnese, “Neuroendocrine Differentiation in Human Prostatic Carcinoma,” Human Pathology, Vol. 23, 1992, pp. 287-296.

[13]   C. K. Ritchie, G. Thomas, L. R. Andrews, D. J. Tindall and L. A. Fitzpatrick, “Effects of the Calciotrophic Peptides Calcitonin and Parathyroid Hormone on Prostate Cancer Growth and Chemotaxis,” Prostate, Vol. 30, 1997, pp. 183-187.

[14]   M. Iwamura, G. Wu, P. A. Abrahamsson, P. A. di Sant’ Agnese, A. T. K. Cockett and L. J. Deftos, “Parathyroid Hormone-Related Protein Is Expressed by Prostatic Neuroendocrine Cells,” Urology, Vol. 43, 1994, pp. 667-674.

[15]   H. Bonkhoff, N. Wernert, G. Dhom and K. Remberger, “Relation of Endocrine-Paracrine Cells to Proliferation in Normal and Hyperplastic, Neoplastic Human Prostate,” Prostate, Vol. 19, 1991, pp. 91-98.

[16]   P. A. Abrahamsson, L. B. Wadstrom, J. Alumets, S. Falkmer and L. Grimelius, “Peptide Hormone and Serotonin-Immunoreactive Cells in Normal and Hypersplastic Prostate Glands,” Pathology Research and Practice, Vol. 185, 1989, pp. 373-380.

[17]   A. G. Aprikian, K. Han, L. Guy, F. Landry, L. R. Begin and S. Chevalier, “Neuroendocrine Differentiation and Bombesin/Gastrin-Releasing Peptide Family of Neuropeptides in the Progress of Human Prostate Cancer,” The Prostate: Supplement, Vol. 82, 1998, pp. 738-743.

[18]   P. di Sant’Agnese and K. de Mesy Jensen, “Somatostatin and Somatostatin-Like Immunoreactive Endocrine-Paracrine Cells in the Human Prostate Gland,” Archives of Pathology & Laboratory Medicine, Vol. 108, 1984, pp. 693-696.

[19]   J. Hansson and P. A. Abrahamsson, “Neuroendocrine Pathogenesis in Adenocarcinoma of the Prostate,” Annals of Oncology, Vol. 12, No. 3, 2001, pp. 145-152.

[20]   P. A. di Sant’Agnese, “Neuroendocrine Differentiation in Carcinoma of the Prostate Diagnostic, Prognostic, and Therapeutic Implications,” Cancer, Vol. 70, 1992, pp. 254-268.

[21]   P. A. Abrahamsson, “Neuroendocrine Differentiation in Prostatic Carcinoma,” Prostate, Vol. 39, No. 2, 1999, pp. 135-148.

[22]   A. Berruti, L. Dogliotti, A. Mosca, M. Bellina, M. Mari, M. Torta, R. Tarabuzzi, E. Bollito, D. Fontana and A. Angeli, “Circulating Neuroendocrine Markers in Patients with Prostate Carcinoma,” Cancer, Vol. 88, 2000, pp. 2590-2597.

[23]   D. Hirano, T. Jike, Y. Okada, S. Minei, Y. Takimoto and N. Nemoto, “Immunohistochemical and Ultrastructural Features of Neuroendocrine Differentiated Carcinomas of the Prostate: An Immunoelectron Microscopic Study,” Ultrastructural Pathology, Vol. 29, 2005, pp. 367-375.

[24]   H. Bonkhoff, “Neuroendocrine Cells in Benign and Malignant Prostate Tissue: Morphogenesis, Proliferation, and Androgen Receptor Status,” Prostate, Supplement 8, 1998, pp. 18-22.

[25]   N. Vashchenko and P. A. Abrahamsson, “Neuroendocrine Differentiation in Prostate Cancer: Implications for New Treatment Modalities,” European Urology, Vol. 47, 2005, pp. 147-155.

[26]   A. van Bokhoven, M. Varella-Garcia, C. Korch, W. U. Johannes, E. E. Smith, H. L. Miller and M. S. Lucia, “Molecular Characterization of Human Prostate Carcinoma Cell Lines,” Prostate, Vol. 57, 2003, pp. 205-225.

[27]   J. Huang, J. L. Yao, P. A. di Sant’Agnese, Q. Yang, P. A. Bourne and Y. Na, “Immunohistochemical Characterization of Neuroendocrine Cells in Prostate Cancer,” Prostate, Vol. 66, 2006, pp. 1399-1406.

[28]   N. Xing, J. Qian, D. Bostwick, E. bergstralh and C. Y. F. Young, “Neuroendocrine Cells in Human Prostate Over-express the Anti-Apoptosis Protein Surviving,” Prostate, Vol. 48, 2001, pp. 7-15.

[29]   C. G. Sauer, A. Roemer and R. Grobholz, “Genetic Analysis of Neuroendocrine Tumour Cells in Prostatic Carcinoma,” Prostate, Vol. 66, 2006, pp. 227-234.

[30]   Y. Xue, A. Verhofstad, W. Lange, F. Smedts, F. Debruyne, J. de la Rosette and J. Schalken, “Prostatic Neuroendocrine Cells Have a Unique Keratin Expression Pattern and Do Not Express Bcl-2: Cell Kinetic Features of Neuroendocrine Cells in the Human Prostate,” American Journal of Pathology, Vol. 151, 1997, pp. 1759-1765.

[31]   P. A. di Sant’Agnese, “Neuroendocrine Differentiation in Prostatic Carcinoma: An Update on Recent Developments,” Annals of Oncology, Vol. 12, Supplement 2, 2001, pp. 135-140.

[32]   A. H. R. Ismail, F. Landry, A. G. Aprikian and S. Chevalier, “Androgen Ablation Promotes Neuroendocrine Cell Differentiation in Dog and Human Prostate,” Prostate, Vol. 51, 2002, pp. 117-125.

[33]   D. Hirano, Y. Okada, S. Minei, Y. Takimoto and N. Nemoto, “Neuroendocrine Differentiation in Hormone Refractory Prostate Cancer Following Androgen Deprivation Therapy,” European Urology, Vol. 45, 2004, pp. 586-592.

[34]   T. C. Yuan, S. Veeramani and M. F. Lin, “Neuroendocrine-Like Prostate Cancer Cells: Neuroendocrine Transdifferentiation of Prostate Adenocarcinoma Cells,” Endocrine-Related Cancer, Vol. 14, 2007, pp. 531-547.

[35]   P. D. Deeble, D. J. Murphy, S. J. Parsons and M. E. Cox, “Interleukin-6- and Cyclic AMP-Mediated Signaling Potentiates Neuroendocrine Differentiation of LNCaP Prostate Tumor Cells,” Molecular and Cellular Biology, Vol. 21, 2001, pp. 8471-8482.

[36]   X. Q. Zhang, D. Kondrikov, T. C. Yuan, F. F. Lin, J. Hansen and M. F. Lin, “Receptor Protein Tyrosine Phosphatase Alpha Signaling Is Involved in Androgen Depletion-Induced Neuroendocrine Differentiation of Androgen-Sensitive LNCaP Human Prostate Cancer Cells,” Oncogene, Vol. 22, 2003, pp. 6704-6716.

[37]   T. C. Yuan, S. Veeramanin, F. F. Lin, D. Kondrikou, S. Zelivianski, T. Igawa, D. Karan, S. K. Batra and M. F. Lin, “Androgen Deprivation Induces Human Prostate Epithelial Neuroendocrine Differentiation of Androgen-Sensitive LNCaP Cells,” Endocrine-Related Cancer, Vol. 13, 2006, pp. 151-167.

[38]   J. T. Arnold and J. T. Isaacs, “Mechanisms Involved in the Progression of Androgen-Independent Prostate Cancers: It Is Not Only the Cancer Cell’s Fault,” Endocrine-Related Cancer, Vol. 9, 2002, pp. 61-73.

[39]   W. J. Huss, C. V. Gregory and G. J. Smith, “Neuroendocrine Cell Differentiation in the CWR33 Human Prostate Cancer Xenograft: Association with Tumor Cell Proliferation Prior to Recurrence,” Prostate, Vol. 60, 2004, pp. 91-97.

[40]   E. C. Nelson, A. J. Cambio, J. C. Yang, J. H. Ok, P. N. Lara Jr. and C. P. Evans, “Clinical Implications of Neuroendocrine Differentiation in Prostate Cancer,” Prostate Cancer and Prostatic Diseases, Vol. 10, 2007, pp. 6-14.

[41]   J. Huang and P. A. di Sant’Agnese, “Neuroendocrine Differentiation in Prostate Cancer: An Overview. Advances in Oncology. The Expanding Role of Octreotide,” BioScientifica Ltd., Bristol, 2002.

[42]   G. R. Cunha, S. W. Hayward, R. Dahiya and B. A. Foster, “Smooth Muscle-Epithelial Interactions in Normal and Neoplastic Prostatic Development,” Acta Anatomica, Vol. 155, 1996, pp. 63-72.

[43]   Y. C. Wong and Y. Z. Wang, “Growth Factors and Epithelial-Stromal Interactions in Prostate Cancer Development,” International Review of Cytology, Vol. 199, 2000, pp. 65-116.

[44]   A. T. Weeraratna, J. T. Arnold, D. J. George, A. DeMarzo and J. T. Isaacs, “Rational Basis for Trk Inhibition Therapy for Prostate Cancer,” Prostate, Vol. 45, 2000, pp. 140-148.

[45]   M. H. Bohrer and J. Schmoll, “Immunohistochemical and Morphometric Studies on Neuroendocrine Differentiation of Prostate Adenocarcinomas,” Verhandlungen der Deutschen Gesellschaft für Pathologie, Vol. 77, 1993, pp. 107-110.

[46]   S. Isshiki, K. Akakura, A. Komiya, H. Suzuki, N. Kamiya and H. Ito, “Chromogranin A Concentration as a Serum Marker to Predict Prognosis after Endocrine Therapy for Prostate Cancer,” Journal of Urology, Vol. 167, 2002, pp. 512-515.

[47]   M. Iwamura, P. A. di Sant’Agnese, G. Wu, C. M. Benning, A. T. Cockett, L. J. Deftos and P. A. Abrahamsson, “Immunohistochemical Localization of Parathyroid Hormone-Related Protein in Human Prostate Cancer,” Cancer Research, Vol. 53, 1993, pp. 1724-1726.

[48]   R. J. Jin, W. Yongqing, N. Masumori, I. Kenichiro, T. Tsukamoto, S. B. Shappell, S. W. Hayward, S. Kasper and R. J. Matusik, “NE-10 Neuroendocrine Cancer Promotes the LNCaP Xenograft Growth in Castrated Mice,” Cancer Research, Vol. 64, 2004, pp. 5489-5495.

[49]   A. J. Raffo, H. Perlman, M. W. Chen, M. L. Day, J. S. Streitman and R. Buttyan, “Overexpression of Bcl-2 Protects Prostate Cancer Cells from Apoptosis in Vitro and Confers Resistance to Androgen Depletion in Vivo,” Cancer Research, Vol. 55, 1995, pp. 4438-4445.

[50]   T. Fixemer, K. Remberger and H. Bonkhoff, “Apoptosis Resistance of Neuroendocrine Phenotypes in Prostatic Adenocarcinoma,” Prostate, Vol. 53, 2002, pp. 118-123.

[51]   T. Yamamoto and N. Tanigawa, “The Role of Survivin as a New Target of Diagnosis and Treatment in Human Cancer,” Medical Electron Microscopy, Vol. 34, 2001, pp. 207-212.

[52]   S. F. Shariat, Y. Lotan, H. Saboorian, S. M. Khoddam, C. G. Roehrborn, K. M. Slawin and R. Ashfaq, “Survivin Expression Is Associated with Features of Biologically Aggressive Prostate Carcinoma,” Cancer, Vol. 100, 2004, pp. 751-757.

[53]   C. Koch-Brandt and C. Morgans, “Clusterin: A Role in Cell Survival in the Face of Apoptosis?” Progress in Molecular and Subcellular Biology, Vol. 16, 1996, pp. 130-149.

[54]   J. Vilches, M. Salido, E. Fernandez-Segura and G. M. Roomans, “Neuropeptides, Apoptosis and Ion Changes in Prostate Cancer. Methods of Study and Recent Developments,” Histology and Histopathology, Vol. 19, 2004, pp. 951-961.

[55]   R. Mazzucchelli, A. Lopez-Beltran, M. Scarpelli and R. Montironi, “Predictive Factors in Prostate Needle Biopsy,” Pathologica, Vol. 94, 2002, pp. 331-337.

[56]   D. Singh, P. G. Febbo and K. Ross, “Gene Expression Correlates of Clinical Prostate Cancer Behaviour,” Cancer Cell, Vol. 1, 2002, pp. 203-209.

[57]   R. Ischia, A. Hobisch, R. Bauer, U. Weiss, R. W. Gasser, W. Horninger, G. Bartsch Jr., D. Fuchs, G. Bartsch, H. Winkler, H. locker, R. Fischer-Colbrie and Z. Culig, “Elevated Levels of Serum Secretoneurin in Patients with Therapy Resistant Carcinoma of the Prostate,” Journal of Urology, Vol. 163, 2000, pp. 1161-1165.

[58]   M. Yashi, A. Nukui, S. Kurokawa, M. Ochi, S. Ishikawa, K. Goto, Y. Kobayashi, O. Muraishi and A. Tokue, “Elevated Serum Progastrin-Releasing Peptide (31 - 98) Level Is a Predictor of Short Response Duration after Hormonal Therapy in Metastatic Prostate Cancer,” Prostate, Vol. 56, 2003, pp. 305-312.

[59]   S. J. Sim, A. B. Glassman, J. Y. Ro, J. J. Lee, C. J. Logothetis and F. J. Liu, “Serum Calcitonin in Small Cell Carcinoma of the Prostate,” Annals of Clinical & Laboratory Science, Vol. 26, 1996, pp. 487-495.

[60]   V. Adamo, L. Noto, T. Franchina, G. Chiofalo, M. Picciotto, G. Toscano and N. Caristi, “Emerging Targeted Therapies for Castration-Resistant Prostate Cancer,” Frontiers in Endocrinology, Vol. 3, 2012, pp. 1-11.

[61]   S. Detchokul and A. G. Frauman, “Recent Developments in Prostate Cancer Biomarker Research: Therapeutic Implications,” British Journal of Pharmacology, Vol. 71, 2011, pp. 157-174.

[62]   W. P. Harris, E. A. Mostaghel, P. S. Nelson and B. Montgomery, “Androgen Deprivation Therapy: Progress in Understanding Mechanisms of Resistance and Optimizing Androgen Depletion,” Nature Clinical Practice Urology, Vol. 6, No. 2, 2009, pp. 76-85.

 
 
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