Neurogenic origin of human prostate endocrine cells

Aumüller, Gerhard; Leonhardt, Markus; Janssen, Michael H.; Konrad, Lutz; Bjartell, Anders; Abrahamsson, Per‐Anders

doi:10.1016/s0090-4295(98)00631-1

Cited by 86 publications

(46 citation statements)

References 22 publications

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“…In our experiments, neuroendocrine cells could secrete PAP and probably serotonin, which has been characterized to be a mitogenic factor and the expression of which is correlated with a poor prognosis (41). The situation seems to be somehow quite different in normal human prostate tissues where neuroendocrine cells do not express any of the PAP and PSA epithelial markers (42). The role of PAP during the pathological development of the prostate cancer is not clear due to the presence of two different forms of PAP, with different physicochemical properties (cPAP and sPAP).…”

Section: Discussionmentioning

confidence: 60%

CaV3.2 T-type Calcium Channels Are Involved in Calcium-dependent Secretion of Neuroendocrine Prostate Cancer Cells

Gackière

Bidaux

Delcourt

et al. 2008

Journal of Biological Chemistry

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Because prostate cancer is, in its early stages, an androgen-dependent pathology, treatments aiming at decreasing testosterone plasma concentration have been developed for many years now. However, a significant proportion of patients suffer a relapse after a few years of hormone therapy. The androgenindependent stage of prostate cancer has been shown to be associated with the development of neuroendocrine differentiation. We previously demonstrated that neuroendocrine prostate cancer cells derived from LNCaP cells overexpress CaV3.2 T-type voltage-dependent calcium channels. We demonstrate here using prostatic acid phosphatase as a marker of prostate secretion and FM1-43 fluorescence imaging of membrane trafficking that neuroendocrine differentiation is associated with an increase in calcium-dependent secretion which critically relies on CaV3.2 T-type calcium channel activity. In addition, we show that these channels are expressed by neuroendocrine cells in prostate cancer tissues obtained from patients after surgery. We propose that CaV3.2 T-type calcium channel up-regulation may account for the alteration of secretion during prostate cancer development and that these channels, by promoting the secretion of potential mitogenic factors, could participate in the progression of the disease toward an androgen-independent stage.Prostate cancer is, in its early stages, an androgen-dependent pathology, meaning that its progression relies on the presence of active steroid male hormones. Treatments developed for many years have been based on this characteristic feature of prostate cancer and, thus, aimed at decreasing the plasma concentration of testosterone or dihydrotestosterone, the prostate active androgen. Although these treatments are particularly valuable in the early development of the disease, leading to the regression of cancers, about a third of the patients suffer a relapse after a few years of hormone therapy. At this stage of hormone refractory disease, deprivation of androgens has no further incidence on the growth of the prostate cancer, and no curative therapy is currently effective (for review, see Ref. 1).The androgen-independent stage of prostate cancer has been shown to be associated with, among others, the development of neuroendocrine differentiation (2). These neuroendocrine features include the appearance of neuroendocrine cell foci surrounded by proliferating epithelial cells (3). Because neuroendocrine prostate cells in normal, hyperplastic, or cancerous tissue secrete many neuropeptides with mitogenic activities like parathyroid hormone-related peptide, calcitonin, or gastrin-related peptides, it has been proposed that paracrine secretion of neurosecretory products released by neuroendocrine cells could be responsible for the progression of cancer toward an androgen-independent stage (for review, see Ref. 4). Indeed, it has been shown for instance that the expression of neuroendocrine markers like chromogranin A is correlated with tumor dedifferentiation (5) and that the presence of neuroendo...

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Section: Discussionmentioning

confidence: 60%

CaV3.2 T-type Calcium Channels Are Involved in Calcium-dependent Secretion of Neuroendocrine Prostate Cancer Cells

Gackière

Bidaux

Delcourt

et al. 2008

Journal of Biological Chemistry

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“…The former cells are considered to be the precursors of the latter ones (Aumüller 1991;Signoretti and Loda 2006). It is of note that a third, minor population of cells, the so-called neuroendocrine cells of neurogenic origin with unresolved physiological function, has also been described in the prostatic glandular epithelium (Noordzij et al 1995;Aumüller et al 1999).…”

Section: Expression Of Prominin-1 and Prominin-2 In The Murine Epididmentioning

confidence: 99%

Robust expression of Prominin-2 all along the adult male reproductive system and urinary bladder

Jászai

Fargeas

Haase

et al. 2008

Histochem Cell Biol

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Although the male reproductive system seems to be enriched in transcripts encoding for both Prominin genes, little is known about their spatial distribution in distinct segments of this organ system. This is especially true for the less-characterized second Prominin paralogue, Prominin-2. The present study, therefore, mainly examines the expression of Prominin-2 in male mice and reveals the existence of some crucial diVerences in the tissue compartmentalization of the two Prominin paralogues in the testis, epididymis, seminal vesicle, prostate and urinary bladder. Our in situ hybridization analysis demonstrates that the major domains of overlapping expression between the two Prominin genes are those compartments that are derived ontogenetically from the epigonadal mesonephric tubules, i.e. ductuli eVerentes, or from the WolYan-tube/ductus mesonephricus, for instance the corpus epididymidis and vesicula seminalis. In contrast, the sinus urogenitalis derivative urinary bladder epithelium expresses exclusively Prominin-2, but not Prominin-1 (CD133). The testis expresses only Prominin-1, not Prominin-2. In human prostate, we Wnally demonstrate that the expression of Prominin-2 (transcript and protein) is highly enriched in cells located in the basal compartment of the glandular epithelium where only a minute population was recently reported to be Prominin-1 positive. Taken together our data indicate that, except for the gonad, Prominin-2 is widely and abundantly expressed along the epithelia of various segments of the adult male genitourinary tract.

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“…1C) (Aumuller et al 1999). To study the PrSCs and better define their differentiation mechanism, recent efforts have focused on the development of efficient in vitro and in vivo assays.…”

Section: In Vivo Regeneration Assaymentioning

confidence: 99%

Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression

Lukacs¹,

Lawson²,

Long-zuo³

et al. 2008

Cold Spring Harbor Symposia on Quantitative Biology

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Prostate cancer is a leading cause of cancer-related death in adult men. It can regress dramatically upon antihormonal therapy, but it often recurs in a more aggressive, androgen-independent form. Defining the prostate tissue stem cells (PrSCs) and their involvement in cancer initiation and maintenance may lead to better therapeutics. Using a tissue-regeneration model in which dissociated prostate epithelial cells mixed with inductive mesenchyme give rise to prostatic tubules, we have identified a small population of prostate cells that contains multiple stem cell characteristics. In this system, prostate cancer can be initiated by autocrine or paracrine growth factor signaling and intracellular overexpression of genes often found mutated in human prostate cancer. Using an in vitro prostate sphere assay, we further defined the PrSC population and demonstrated their selfrenewal and multilineage differentiation capabilities. Microarray analyses of the stem-and non-stem-cell populations have assisted us in finding and evaluating additional markers that can better define the PrSC population and further delineate the different cell types of the prostate, including those that serve as the target cell for tumor initiation.

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Neurogenic origin of human prostate endocrine cells

Cited by 86 publications

References 22 publications

CaV3.2 T-type Calcium Channels Are Involved in Calcium-dependent Secretion of Neuroendocrine Prostate Cancer Cells

CaV3.2 T-type Calcium Channels Are Involved in Calcium-dependent Secretion of Neuroendocrine Prostate Cancer Cells

Robust expression of Prominin-2 all along the adult male reproductive system and urinary bladder

Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression

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