Prostatic ductal system in rats: Changes in regional distribution of extracellular matrix proteins during castration-induced regression

Ilio, Kenneth Y.; Nemeth, Jeffrey A.; Sensibar, Julia A.; Lang, Sharon; Lee, Chung

doi:10.1002/(sici)1097-0045(20000401)43:1<3::aid-pros2>3.0.co;2-j

Cited by 20 publications

(22 citation statements)

References 27 publications

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“…Because mouse epithelial cells with this property were not available, we determined Notch1 expression levels in human prostate epithelial cells (PrEC) (23,24), and we compared it with the levels in human prostate epithelial organoid, which is composed of mainly luminal epithelial cells and some parenchymal cells (27), and in the BPH-1 cells (26) using quantitative Taqman real time RT-PCR. PrEC have been extensively used in prostate research and are generally believed to represent proliferating basal cell populations of human adult prostate, as these cells are derived from mature prostatic epithelium and are maintained in the absence of androgen, which favors the selection of proliferating basal cells (23,35). As shown in Fig.…”

Section: Notch1-expressing Cells In Prostate Development and Re-growthsupporting

confidence: 82%

Notch1-expressing Cells Are Indispensable for Prostatic Branching Morphogenesis during Development and Re-growth Following Castration and Androgen Replacement

Wang

Shou

Wong³

et al. 2004

Journal of Biological Chemistry

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Notch expression is frequently associated with progenitor cells, and its function is crucial for development. Our recent work showing that Notch1 is selectively expressed in basal epithelial cells of the prostate and higher Notch1 expression during development suggests that Notch1-expressing cells may define progenitor cells in the prostate. To test this hypothesis, we have generated a transgenic mouse line in which the Notch1-expressing cells can be ablated in a controlled manner. Specific targeting was achieved by expressing the bacterial nitroreductase, an enzyme that catalyzes its substrate into a cytotoxin capable of inducing apoptosis, under the Notch1 promoter. Cell death in transgenic prostate was confirmed by histological analyses including terminal dUTP nick-end labeling and caspase 3 immunocytochemical staining. We evaluated the consequences of ablation of Notch1-expressing cells in two systems, organ culture of early postnatal prostates and re-growth of prostate in castrated mice triggered by hormone replacement. Our data show that elimination of Notch1-expressing cells inhibited the branching morphogenesis, growth, and differentiation of early postnatal prostate in culture and impaired prostate re-growth triggered by hormone replacement in castrated mice. Furthermore, we found that Notch1 expression following castration and hormone replacement was concomitant with known basal cell markers p63 and cytokeratin 14 and was high in the proliferative human prostate epithelial cells. Taken together, these data suggest that Notch1-expressing cells define the progenitor cells in the prostatic epithelial cell lineage, which are indispensable for prostatic development and re-growth.

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Section: Notch1-expressing Cells In Prostate Development and Re-growthsupporting

confidence: 82%

Notch1-expressing Cells Are Indispensable for Prostatic Branching Morphogenesis during Development and Re-growth Following Castration and Androgen Replacement

Wang

Shou

Wong³

et al. 2004

Journal of Biological Chemistry

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“…Herein, the location of matrilysin just below epithelium is also colocalized with residual epithelial BM and suggests that MMP-7 participates in the degradation of some epithelial BM components resulting in an interrupted pattern of type IV collagen and chondroitin sulfate distribution in the involuting rat prostate (Ilio et al, 2000;Terry and Clark, 1996). Furthermore, MMP-7 might participate in the remodeling of collagen fibers associated with glandular atrophy induced by androgen ablation, mainly the reticular fibers (Vilamaior et al, 2000).…”

Section: Discussionmentioning

confidence: 80%

Epithelial‐stromal transition of MMP‐7 immunolocalization in the rat ventral prostate following bilateral orchiectomy

Felisbino¹,

Justulin²,

Carvalho³

et al. 2007

Cell Biology International

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Epithelial cells from involuting rat ventral prostate (VP) express Matrilysin (MMP-7) mRNA. Herein, we investigated by immunohistochemistry the MMP-7 protein location and its association with tissue changes following castration in the VP. Normal and castrated adult male Wistar rats were sacrificed at different times after surgery. VP was examined by immunocytochemistry and immunoprecipitation. Castration promoted a shrinking of prostate ducts with an extensive stromal remodeling. In the VP from normal rats, MMP-7 immunoreactivity was found in epithelial secretory granules. Three days after castration, immunostaining for MMP-7 was found in both the epithelial secretory granules and in the stroma just below the epithelium, mainly at the distal ductal tips. At seven and 21 days after castration, the immunostaining for MMP-7 was found only in the stromal space. Immunoprecipitation confirmed the specificity of the primary antibody by rescuing a pro-enzyme form (28kDa) in the prostate extracts. The present results suggest that MMP-7 participates in the epithelial-stromal interface remodeling of the ventral prostate during the involution achieved by castration, probably in the degradation of components of the epithelial basement membrane.

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“…These changes at the ultrasctructural level may have implications for prostate growth in normal and pathologic states, though mechanistic cause-effect studies will be required to confirm this hypothesis. In this context, collagen type IV has been shown to enhance the growth of rat ventral prostatic epithelial cells in vitro [69], and type I collagen mediates proliferative responses of prostate carcinoma cells [70].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Aging on the Molecular and Cellular Composition of the Prostate Microenvironment

et al. 2010

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BackgroundAdvancing age is associated with substantial increases in the incidence rates of common diseases affecting the prostate gland including benign prostatic hyperplasia (BPH) and prostate carcinoma. The prostate is comprised of a functional secretory epithelium, a basal epithelium, and a supporting stroma comprised of structural elements, and a spectrum of cell types that includes smooth muscle cells, fibroblasts, and inflammatory cells. As reciprocal interactions between epithelium and stromal constituents are essential for normal organogenesis and serve to maintain normal functions, discordance within the stroma could permit or promote disease processes. In this study we sought to identify aging-associated alterations in the mouse prostate microenvironment that could influence pathology.Methodology/Principal FindingsWe quantitated transcript levels in microdissected glandular-adjacent stroma from young (age 4 months) and old (age 20–24 months) C57BL/6 mice, and identified a significant change in the expression of 1259 genes (p<0.05). These included increases in transcripts encoding proteins associated with inflammation (e.g., Ccl8, Ccl12), genotoxic/oxidative stress (e.g., Apod, Serpinb5) and other paracrine-acting effects (e.g., Cyr61). The expression of several collagen genes (e.g., Col1a1 and Col3a1) exhibited age-associated declines. By histology, immunofluorescence, and electron microscopy we determined that the collagen matrix is abundant and disorganized, smooth muscle cell orientation is disordered, and inflammatory infiltrates are significantly increased, and are comprised of macrophages, T cells and, to a lesser extent, B cells.Conclusion/SignificanceThese findings demonstrate that during normal aging the prostate stroma exhibits phenotypic and molecular characteristics plausibly contributing to the striking age associated pathologies affecting the prostate.

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Prostatic ductal system in rats: Changes in regional distribution of extracellular matrix proteins during castration-induced regression

Cited by 20 publications

References 27 publications

Notch1-expressing Cells Are Indispensable for Prostatic Branching Morphogenesis during Development and Re-growth Following Castration and Androgen Replacement

Notch1-expressing Cells Are Indispensable for Prostatic Branching Morphogenesis during Development and Re-growth Following Castration and Androgen Replacement

Epithelial‐stromal transition of MMP‐7 immunolocalization in the rat ventral prostate following bilateral orchiectomy

The Effects of Aging on the Molecular and Cellular Composition of the Prostate Microenvironment

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