Proliferative activity and branching morphogenesis in the human prostate: A closer look at pre‐ and postnatal prostate growth

Xue, Yong; Sonke, Gabe S.; Schoots, Coen; Schalken, Jack A.; Verhofstad, A.A.J.; Rosette, Jean de la; Smedts, Frank

doi:10.1002/pros.1127

Cited by 23 publications

(15 citation statements)

References 25 publications

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“…In contrast, our lineage tracking of mtDNA mutations suggests that acinar fission is rarely observed in the adult prostate. Budding tips are the major growth foci during early prostate development 29, and the findings in the ageing prostate perhaps reflect the relatively slower nature of epithelial turnover, permitting multi‐focal accumulation of random mtDNA mutations to high levels of heteroplasmy which spread to the progeny of stem cells in their proximity only. Therefore, in the prostate, it is implied that multiple mutations are acquired stochastically as independent events 30, as opposed to monoclonal conversion or gland/acinus fission as seen in other epithelial organs 15.…”

Section: Discussionmentioning

confidence: 99%

In situ lineage tracking of human prostatic epithelial stem cell fate reveals a common clonal origin for basal and luminal cells

Blackwood

Williamson

Greaves

et al. 2011

The Journal of Pathology

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Stem cells accumulate mitochondrial DNA (mtDNA) mutations resulting in an observable respiratory chain defect in their progeny, allowing the mapping of stem cell fate. There is considerable uncertainty in prostate epithelial biology where both basal and luminal stem cells have been described, and in this study the clonal relationships within the human prostate epithelial cell layers were explored by tracing stem cell fate. Fresh-frozen and formalin-fixed histologically-benign prostate samples from 35 patients were studied using sequential cytochrome c oxidase (COX)/succinate dehydrogenase (SDH) enzyme histochemistry and COX subunit I immunofluorescence to identify areas of respiratory chain deficiency; mtDNA mutations were identified by whole mitochondrial genome sequencing of laser-captured areas. We demonstrated that cells with respiratory chain defects due to somatic mtDNA point mutations were present in prostate epithelia and clonally expand in acini. Lineage tracing revealed distinct patterning of stem cell fate with mtDNA mutations spreading throughout the whole acinus or, more commonly, present as mosaic acinar defects. This suggests that individual acini are typically generated from multiple stem cells, and the presence of whole COX-deficient acini suggests that a single stem cell can also generate an entire branching acinar subunit of the gland. Significantly, a common clonal origin for basal, luminal and neuroendocrine cells is demonstrated, helping to resolve a key area of debate in human prostate stem cell biology.

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Section: Discussionmentioning

confidence: 99%

In situ lineage tracking of human prostatic epithelial stem cell fate reveals a common clonal origin for basal and luminal cells

Blackwood

Williamson

Greaves

et al. 2011

The Journal of Pathology

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“…In the developmental process, human prostate epithelial cells undergo two waves of proliferation: at early embryonic morphogenesis and during early young adulthood (20,21). Proliferative activity in the epithelial compartment is sustained during reproductive ages but declines with age, and in later life, only a basal level of epithelial proliferation is seen.…”

Section: Discussionmentioning

confidence: 99%

PrLZ Is Expressed in Normal Prostate Development and in Human Prostate Cancer Progression

Wang

Mabjeesh

et al. 2007

Clinical Cancer Research

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Purpose: We previously reported the isolation and characterization of PrLZ, a novel prostatespecific and androgen-responsive gene of the tumor protein D52 family at chromosome 8q21.1. PrLZ is the only known gene in this locus with prostate specificity. Expression level of PrLZ was elevated specifically in cancer cells, suggesting its association with malignancy. Experimental Design:To define its biological function in the morphogenesis, development, and functional maturation of the prostate gland and to gain further insight into its role in prostate cancer, we examined PrLZ expression in prostate specimens during early embryonic development and in adult tissue. Results: PrLZ first appears in the nuclei of the prostate epithelia at 16 weeks of gestation before its distribution in the cytoplasm at later ages. Its expression peaks at 24 years of age, declines at 31years of age, and maintains a minimal level in later age. On prostate cancer development, PrLZ expression is reactivated, and its expression increases from primary localized tumor to bone metastasis. Overexpression of PrLZ in prostate cancer cells accelerates their growth in vitro and tumor formation in vivo. Conclusion: This work identifies PrLZ as a marker for prostate cancer progression and metastasis, andits pattern of expression is suggestive of a proto-oncogene.

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“…One hypothesis about the initiating event in BPH, and possibly the beginning of neoplastic transformation, suggests that glandular budding and branching may be reactivated in the adult prostate (McNeal, 1978(McNeal, , 1988. Such reactivated branching activity was demonstrated in the adult prostate (Xue et al, 2001). …”

Section: Introductionmentioning

confidence: 99%

Identification of a stem cell candidate in the normal human prostate gland

Schmelz

Moll

Hesse

et al. 2005

European Journal of Cell Biology

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Stem cells of the human prostate gland have not yet been identified utilizing a structural biomarker. We have discovered a new prostatic epithelial cell phenotype-expressing cytokeratin 6a (Ck6a+ cells). The Ck6a+ cells are present within a specialized niche in the basal cell compartment in fetal, juvenile and adult prostate tissue, and within the stem cell-enriched urogenital sinus. In adult normal prostate tissue, the average abundance of Ck6a+ cells was 4.9%. With proliferative stimuli in the prostate organ culture model, in which the epithelial-stromal interaction was maintained, a remarkable increase of Ck 6a expression was noticed to up to 64.9%. The difference in cytokeratin 6a expression between the normal adult prostate and the prostate organ culture model was statistically significant (p<0.0001). Within the prostate organ culture model the increase of cytokeratin 6a-expressing cells significantly correlated with increased proliferation index (r = 0.7616; p = 0.0467) The Ck6a+ cells were capable of differentiation as indicated by their expression of luminal cell markers such as ZO-1 and prostate specific antigen (PSA). Our data indicate that Ck6a+ cells represent a prostatic epithelial stem cell candidate possessing high potential for proliferation and differentiation. Since the development of benign prostatic hyperplasia and prostate carcinogenesis are disorders of proliferation and differentiation, the Ck6a+ cells may represent a major element in the development of these diseases.

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Proliferative activity and branching morphogenesis in the human prostate: A closer look at pre‐ and postnatal prostate growth

Cited by 23 publications

References 25 publications

In situ lineage tracking of human prostatic epithelial stem cell fate reveals a common clonal origin for basal and luminal cells

In situ lineage tracking of human prostatic epithelial stem cell fate reveals a common clonal origin for basal and luminal cells

PrLZ Is Expressed in Normal Prostate Development and in Human Prostate Cancer Progression

Identification of a stem cell candidate in the normal human prostate gland

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