The Neuroendocrine Cell Population of the Human Prostate Gland

Cohen, Ronald J.; Glezerson, Graham; Taylor, Lewis; Grundle, Helene A.J.; Naudé, Johan

doi:10.1016/s0022-5347(17)35484-8

Cited by 68 publications

(47 citation statements)

References 13 publications

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“…Immunohistochemic analysis showed PAMP-and PAM-immunoreactive cells distributed with patterns similar to other NE markers in the normal 32 and malignant 6 prostate. Both types of immunoreactive cell are subpopulations of NE CgA-expressing cells.…”

Section: Discussionmentioning

confidence: 75%

Peptidylglycine ?-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate

Jiménez¹,

Jongsma²,

Calvo³

et al. 2001

Int. J. Cancer

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Most PCs show NE differentiation. Several studies have tried to correlate NE expression with disease status, but the reported findings have been contradictory. Prostatic NE cells synthesize peptides with a wide spectrum of potential functions. Some of these active peptides, such as PAMP, are amidated. PAM is the only carboxy-terminal peptide-amidating enzyme identified. We studied expression of PAMP and PAM in normal prostate and prostatic tumors (clinical specimens and human xenograft models) with or without prior androgen-deprivation therapy and found a wide distribution of both molecules in NE subpopulations of all kinds. Although the correlation of either marker to tumor grade, clinical progression or disease prognosis did not reach statistical significance, PAMP-or PAM-immunoreactive cells were induced after androgen-blockade therapy. In the PC-310 and PC-295 androgen-dependent models, PAMP or PAM NE differentiation was induced after castration in different ways, being higher in PC-310, which might explain its long-term survival after androgen deprivation. We show induction of expression of 2 new NE markers in clinical specimens and xenografted PC after endocrine therapy.

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Section: Discussionmentioning

confidence: 75%

Peptidylglycine ?-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate

Jiménez¹,

Jongsma²,

Calvo³

et al. 2001

Int. J. Cancer

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“…Like other visceral tissues in the human body, the adult prostate gland contains a small fraction of neuroendocrine cells dispersed throughout the epithelial cell layer (30). These cells have a unique morphology that includes the presence of a large number of dense intracellular secretory granules that store a diverse collection of neurosecretory peptides (exemplified by bombesin, calcitonin, parathyroid-like hormone, serotonin, and proadrenomedullin) that have the potential to influence the growth and survival of other epithelial cells in which they are interspersed.…”

Section: Discussionmentioning

confidence: 99%

A Human- and Male-Specific Protocadherin that Acts through the Wnt Signaling Pathway to Induce Neuroendocrine Transdifferentiation of Prostate Cancer Cells

et al. 2005

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Protocadherin-PC (PCDH-PC) is a gene on the human Y chromosome that is selectively expressed in apoptosis-and hormone-resistant human prostate cancer cells. The protein encoded by PCDH-PC is cytoplasmically localized and has a small serine-rich domain in its COOH terminus that is homologous to the B-catenin binding site of classical cadherins. Variants of prostate cancer cells that express PCDH-PC have high levels of nuclear B-catenin protein and increased wnt-signaling. In this study, we show that transfection of human prostate cancer cells (LNCaP) with PCDH-PC or culture of these cells in androgen-free medium (a condition that up-regulates PCDH-PC expression) activates wnt signaling as assessed by nuclear accumulation of B-catenin, increased expression of luciferase from a reporter vector promoted by Tcf binding elements and increased expression of wnt target genes. Moreover, LNCaP cells transfected with PCDH-PC or grown in androgen-free medium transdifferentiate to neuroendocrine-like cells marked by elevated expression of neuron-specific enolase and chromogranin-A. Neuroendocrine transdifferentiation was also observed when LNCaP cells were transfected by stabilized B-catenin. Increased wnt signaling and neuroendocrine transdifferentiation of LNCaP cells induced by culture in androgen-free medium was suppressed by short interfering RNAs that target PCDH-PC as well as by dominant-negative Tcf or short interfering RNA against B-catenin, supporting the hypothesis that increased expression of PCDH-PC is driving neuroendocrine transdifferentiation by activating wnt signaling. These findings have significant implications for the process through which prostate cancers progress to hormone resistance in humans. (Cancer Res 2005; 65(12): 5263-71)

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“…1F). Basal cells in benign human prostate glands are the dividing or progenitor cell (a subset of which may be the true prostatic "stem cells"), giving rise to the differentiated secretory cells lining the gland lumens and, most likely, to NE cells as well (21,23). Basal cells tend to be oriented parallel to the basement membrane, are not always conspicuous by light microscopy, and can be difficult to distinguish from underlying spindle stromal cells (6).…”

Section: Histology and Phenotype Of Human Prostate Glandsmentioning

confidence: 99%

“…9) Definition. NE Carcinoma [23]. NE carcinoma in GEM prostate is an invasive malignant epithelial neoplasm that shows light microscopic, immunohistochemical, and ultrastructural features indicative …”

Section: Adenocarcinoma (mentioning

confidence: 99%

Prostate Pathology of Genetically Engineered Mice: Definitions and Classification. The Consensus Report from the Bar Harbor Meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee

et al. 2004

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Among the neoplastic disorders, preinvasive, microinvasive, and poorly differentiated neoplasms received the most attention. Specific criteria were recommended and will be discussed. Transitions between neoplastic states were of particular concern. Preinvasive neoplasias of the mouse prostate were recognized as focal, atypical, and progressive lesions. These lesions were designated as mouse prostatic intraepithelial neoplasia (mPIN). Some atypical lesions were identified in mouse models without evidence of progression to malignancy. The panel recommended that mPIN lesions not be given histological grades, but that mPIN be further classified as to the absence or presence of documented associated progression to invasive carcinoma. Criteria for recognizing microinvasion, for classification of invasive gland-forming adenocarcinomas, and for characterizing poorly differentiated tumors, including neuroendocrine carcinomas, were developed and are discussed. The uniform application of defined terminology is essential for correlating results between different laboratories and models. It is recommended that investigators use the Bar Harbor Classification system when characterizing new GEM models or when conducting experimental interventions that may alter the phenotype or natural history of lesion progression in existing models.

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The Neuroendocrine Cell Population of the Human Prostate Gland

Cited by 68 publications

References 13 publications

Peptidylglycine ?-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate

Peptidylglycine ?-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate

A Human- and Male-Specific Protocadherin that Acts through the Wnt Signaling Pathway to Induce Neuroendocrine Transdifferentiation of Prostate Cancer Cells

Prostate Pathology of Genetically Engineered Mice: Definitions and Classification. The Consensus Report from the Bar Harbor Meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee

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