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

Felisbino, Sérgio Luís; Justulin, Luis Antônio; Carvalho, Hernandes F.; Taboga, Sebastião Roberto

doi:10.1016/j.cellbi.2007.03.034

Cited by 13 publications

(16 citation statements)

References 46 publications

(55 reference statements)

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“…The prostatic stroma has been considered an important compartment due to its role in the maintenance of prostate histoarchitecture, homeostasis and its involvement in prostate diseases such as benign hyperplasia and cancer (Cunha et al, 2002; Chung et al, 2006; Ribeiro et al, 2006; Tuxhorn, 2002; Zhang et al, 2003). Our group has previously demonstrated a major role for the stromal components on prostate morphophysiology in several experimental conditions (Delella et al, 2007; Felisbino et al, 2007; Justulin et al, 2008, 2010; Vilamaior et al, 2000;). Thus, changes in the distribution of collagen fibers by cadmium treatment might affect normal epithelium–stroma interactions leading to changes in prostate homeostasis, which could be a factor in cadmium‐induced prostate carcinogenesis.…”

Section: Discussionmentioning

confidence: 93%

Early changes induced by short‐term low‐dose cadmium exposure in rat ventral and dorsolateral prostates

Lacorte

Delella

Amorim

et al. 2011

Microscopy Res & Technique

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Prostate cancer (PCa) is the most commonly diagnosed cancer in men. The etiology of PCa in humans is multifactorial and includes age, ethnicity, environmental factors, and other unknown causes. Epidemiological and experimental evidence has shown that cadmium is associated with PCa both in humans and rodents. This metal can act as an endocrine disruptor during prostate development, and it induces prostate lesions late in life. In this study, we investigated the effects of low-dose cadmium on rat prostate morphology during puberty. Two-month-old male Wistar rats were randomized into two experimental groups: cadmium-treated and control. The ventral and dorsolateral prostates were dissected, weighed, and immunohistochemically stained with specific antibodies against Ki-67 and the androgen receptor (AR). The concentration of cadmium was measured in the blood and prostate, and testosterone concentration was measured from the plasma. Our results show that cadmium concentration was increased in both the blood and the prostate of cadmium-treated rats, but there were no changes in the prostatic weight, epithelial cell height, or testosterone levels. However, AR immunostaining and epithelial cell proliferation (Ki-67 index) were increased in both prostates with an increase in apoptosis only in the dorsal lobe. Furthermore, atypical hyperplasic proliferative lesions were found in the dorsolateral lobe after cadmium exposure. Cadmium treatment reduced collagen fiber absolute volume in both prostates. Thus, low-doses of cadmium, even for a short period of time, can interfere with prostate epithelium-stroma homeostasis, and this disruption might be an important factor in the onset of prostate lesions late in life.

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Section: Discussionmentioning

confidence: 93%

Early changes induced by short‐term low‐dose cadmium exposure in rat ventral and dorsolateral prostates

Lacorte

Delella

Amorim

et al. 2011

Microscopy Res & Technique

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“…The importance of MMP7 for testicular integrity has been demonstrated by studies with transgenic animals overexpressing MMP7 [59], which presented disintegration of the testicular interstitial tissue and infertility. In the rat prostate, MMP7 is localized to the secretory granules of epithelial cells, but bilateral orchidectomy induces a change in MMP7 localization to the stroma just below the epithelium, suggesting that MMP7 can participate in the remodeling of the epithelial-stroma interface, probably by degradating components of the epithelial basement membrane [61].…”

Section: Discussionmentioning

confidence: 98%

Effects of the Antiestrogen Fulvestrant (ICI 182,780) on Gene Expression of the Rat Efferent Ductules1

Yasuhara

Gomes

Siu

et al. 2008

Biology of Reproduction

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The efferent ductules express the highest amount of estrogen receptors ESR1 (ERalpha) and ESR2 (ERbeta) within the male reproductive tract. Treatment of rats with the antiestrogen fulvestrant (ICI 182,780) causes inhibition of fluid reabsorption in the efferent ductules, leading to seminiferous tubule atrophy and infertility. To provide a more comprehensive knowledge about the molecular targets for estrogen in the rat efferent ductules, we investigated the effects of ICI 182,780 treatment on gene expression using a microarray approach. Treatment with ICI 182,780 increased or reduced at least 2-fold the expression of 263 and 98 genes, respectively. Not surprisingly, several genes that encode ion channels and macromolecule transporters were affected. Interestingly, treatment with ICI 182,780 markedly altered the expression of genes related to extracellular matrix organization. Matrix metalloproteinase 7 (Mmp7), osteopontin (Spp1), and neuronal pentraxin 1 (Nptx1) were among the most altered genes in this category. Upregulation of Mmp7 and Spp1 and downregulation of Nptx1 were validated by Northern blot. Increase in Mmp7 expression was further confirmed by immunohistochemistry and probably accounted for the decrease in collagen content observed in the efferent ductules of ICI 182,780-treated animals. Downregulation of Nptx1 probably contributed to the extracellular matrix changes and decreased amyloid deposition in the efferent ductules of ICI 182,780-treated animals. Identification of new molecular targets for estrogen action may help elucidate the regulatory role of this hormone in the male reproductive tract.

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“…The previous studies demonstrated that androgen exerts differential effect on expression of MMPs between normal and malignant prostate tissue ⁄ cells. For example, in vivo, both androgen ablation (Wilson et al, 1991;Powell et al, 1996;Wilson et al, 2002;Felisbino et al, 2007;Limaye et al, 2008) and androgen replacement (Wilson et al, 1991;Limaye et al, 2008) upregulates MMP mRNA and protein expression in rat ventral prostate. Moreover, in vitro studies using androgendependent prostate cancer LNCaP cells showed that androgen upregulates MMP-2 protein expression, without changes in MMP-9, and with TIMP-2 down regulation (Liao et al, 2003;Li et al, 2007), while androgen receptor signalling increases MMP-2 and MMP-9 activities in MDA cancer cell lines (Hara et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…, 2008). In a previous work, our group demonstrated using immunohistochemistry that after androgen ablation MMP‐7 localization changes from apical region of epithelial cells to the stromal space close to the basement membrane, suggesting that MMP‐7 participates in the epithelial‐stromal interface remodelling of the ventral prostate during the involution achieved by castration (Felisbino et al. , 2007).…”

Section: Introductionmentioning

confidence: 99%

Finasteride treatment alters MMP‐2 and ‐9 gene expression and activity in the rat ventral prostate

Delella¹,

Justulin²,

Felisbino³

2010

Int J of Andrology

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The safety of using finasteride as a prevention of prostate cancer is still under debate. In this study, we investigated the effects of finasteride on the location, gene expression and activities of matrix metalloproteinases -2 and -9, which are involved in the degradation of extracellular matrix components during tissue remodelling and prostate cancer progression, invasion and metastasis. Ventral prostates (VP) from Wistar rats treated with finasteride (25 mg/kg/day) for 7 and 30 days and age-matched controls were evaluated using histology, immunohistochemistry, semi-quantitative RT-PCR and gelatin zymography. Finasteride treatment reduced the epithelial immunostaining of MMP-2 but increased MMP-9 immunostaining in the epithelial cells and in the stroma. The mRNA expression of both MMP-2 and MMP-9 were significantly increased on day 7 of finasteride treatment, mainly for MMP-9 and returned to the control levels by day 30. However, gelatin zymography showed that MMP-9 activity was significantly increased on day 7 of finasteride treatment and remained elevated on day 30 (p < 0.05), while MMP-2 activity was reduced after 30 days of treatment. Finasteride increases MMP-9 and reduces MMP-2 activities in the prostate, which may affect negatively and positively both normal and tumoural prostatic cell behaviour during the treatment. Studies on expression of MMPs in the prostate during different androgen manipulation or cancer chemoprevention strategies can contribute to understand the tissue's overall response and clinical data.

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

Cited by 13 publications

References 46 publications

Early changes induced by short‐term low‐dose cadmium exposure in rat ventral and dorsolateral prostates

Early changes induced by short‐term low‐dose cadmium exposure in rat ventral and dorsolateral prostates

Effects of the Antiestrogen Fulvestrant (ICI 182,780) on Gene Expression of the Rat Efferent Ductules1

Finasteride treatment alters MMP‐2 and ‐9 gene expression and activity in the rat ventral prostate

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