Limits...
Increased SNAIL expression and low syndecan levels are associated with high Gleason grade in prostate cancer.

Poblete CE, Fulla J, Gallardo M, Muñoz V, Castellón EA, Gallegos I, Contreras HR - Int. J. Oncol. (2014)

Bottom Line: Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells.Interestingly, syndecan 2 shows no changes associated to histological grade.It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1.

View Article: PubMed Central - PubMed

Affiliation: Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.

ABSTRACT
Prostate cancer (PC) is a leading male oncologic malignancy wideworld. During malignant transformation, normal epithelial cells undergo genetic and morphological changes known as epithelial-mesenchymal transition (EMT). Several regulatory genes and specific marker proteins are involved in PC EMT. Recently, syndecans have been associated with malignancy grade and Gleason score in PC. Considering that SNAIL is mainly a gene repressor increased in PC and that syndecan promoters have putative binding sites for this repressor, we propose that SNAIL might regulate syndecan expression during PC EMT. The aim of this study was to analyze immunochemically the expression of SNAIL, syndecans 1 and 2 and other EMT markers in a tissue microarray (TMA) of PC samples and PC cell lines. The TMAs included PC samples of different Gleason grade and benign prostatic hyperplasia (BPH) samples, as non‑malignant controls. PC3 and LNCaP cell lines were used as models of PC representing different tumorigenic capacities. Semi-quantitative immunohistochemistry was performed on TMAs and fluorescence immunocytochemistry and western blot analysis were conducted on cell cultures. Results show that SNAIL exhibits increased expression in high Gleason specimens compared to low histological grade and BPH samples. Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells. Conversely, syndecan 1, similarly to E-cadherin (a known marker of EMT), shows a decreased expression in high Gleason grades samples and PC3 cells. Interestingly, syndecan 2 shows no changes associated to histological grade. It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1. The mechanism by which SNAIL regulates the expression of syndecan 1 remains to be investigated.

Show MeSH

Related in: MedlinePlus

Syndecan 1 expression and distribution in prostate samples. Immunostaining of syndecan 1 in samples of different histological grades. (A) Benign prostatic hyperplasia (BPH); (B) low Gleason grade (LGG); (C) medium Gleason grade (MGG) and (D) high Gleason grade (HGG). (E) Quantification of syndecan 1 immunostaining. (F) E-cadherin (epithelial control marker) immunostaining: (a) Benign prostatic hyperplasia (BPH); (b) low Gleason grade (LGG); (c) medium Gleason grade (MGG) and (d) high Gleason grade (HGG). (e) Quantification of E-cadherin immunostaining. Inserts ×1,000. IOD, integrated optical density. AU, arbitrary units. *P<0.01. Scale bar, 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3928469&req=5

f3-ijo-44-03-0647: Syndecan 1 expression and distribution in prostate samples. Immunostaining of syndecan 1 in samples of different histological grades. (A) Benign prostatic hyperplasia (BPH); (B) low Gleason grade (LGG); (C) medium Gleason grade (MGG) and (D) high Gleason grade (HGG). (E) Quantification of syndecan 1 immunostaining. (F) E-cadherin (epithelial control marker) immunostaining: (a) Benign prostatic hyperplasia (BPH); (b) low Gleason grade (LGG); (c) medium Gleason grade (MGG) and (d) high Gleason grade (HGG). (e) Quantification of E-cadherin immunostaining. Inserts ×1,000. IOD, integrated optical density. AU, arbitrary units. *P<0.01. Scale bar, 50 μm.

Mentions: The expression and distribution of syndecan 1 show a very heterogeneous pattern within the groups studied. BPH spots show a strong intensity localized mainly in the cytoplasm and membrane of the basal cells. Furthermore, epithelial cells exhibit a preferential localization in the baso-lateral region and approximately 50% of the cytoplasmic localization is detected at variable intensity (weak to moderate). This syndecan 1 distribution is also found in the low Gleason group and, to a lesser extent, in the medium Gleason group. However, in PC spots with high Gleason grade, membrane localization is lost and a granular cytoplasmic localization with low intensity is observed (Fig. 3). The main difference of this marker among the groups is found in its location. For comparison, E-cadherin (a validated epithelial marker) expression and distribution was evaluated in PC TMA samples. This epithelial marker shows an expected membrane location in most samples with intensities varying from moderate to strong. In BPH spots, E-cadherin shows mainly baso-lateral location in gland epithelial cells and was absent in apical membrane. On the other hand, low Gleason grade samples show syndecan 1 intensity and distribution similar to BPH. However, in high Gleason grade spots, a loss of intensity associated to gland architecture disorganization is observed (Fig. 3E). In addition, E-cadherin distribution shows a mixed pattern including cytoplasm location (Fig. 3F). Significant decrease in E-cadherin expression is observed only in medium and high Gleason grade samples (Fig. 3F).


Increased SNAIL expression and low syndecan levels are associated with high Gleason grade in prostate cancer.

Poblete CE, Fulla J, Gallardo M, Muñoz V, Castellón EA, Gallegos I, Contreras HR - Int. J. Oncol. (2014)

Syndecan 1 expression and distribution in prostate samples. Immunostaining of syndecan 1 in samples of different histological grades. (A) Benign prostatic hyperplasia (BPH); (B) low Gleason grade (LGG); (C) medium Gleason grade (MGG) and (D) high Gleason grade (HGG). (E) Quantification of syndecan 1 immunostaining. (F) E-cadherin (epithelial control marker) immunostaining: (a) Benign prostatic hyperplasia (BPH); (b) low Gleason grade (LGG); (c) medium Gleason grade (MGG) and (d) high Gleason grade (HGG). (e) Quantification of E-cadherin immunostaining. Inserts ×1,000. IOD, integrated optical density. AU, arbitrary units. *P<0.01. Scale bar, 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928469&req=5

f3-ijo-44-03-0647: Syndecan 1 expression and distribution in prostate samples. Immunostaining of syndecan 1 in samples of different histological grades. (A) Benign prostatic hyperplasia (BPH); (B) low Gleason grade (LGG); (C) medium Gleason grade (MGG) and (D) high Gleason grade (HGG). (E) Quantification of syndecan 1 immunostaining. (F) E-cadherin (epithelial control marker) immunostaining: (a) Benign prostatic hyperplasia (BPH); (b) low Gleason grade (LGG); (c) medium Gleason grade (MGG) and (d) high Gleason grade (HGG). (e) Quantification of E-cadherin immunostaining. Inserts ×1,000. IOD, integrated optical density. AU, arbitrary units. *P<0.01. Scale bar, 50 μm.
Mentions: The expression and distribution of syndecan 1 show a very heterogeneous pattern within the groups studied. BPH spots show a strong intensity localized mainly in the cytoplasm and membrane of the basal cells. Furthermore, epithelial cells exhibit a preferential localization in the baso-lateral region and approximately 50% of the cytoplasmic localization is detected at variable intensity (weak to moderate). This syndecan 1 distribution is also found in the low Gleason group and, to a lesser extent, in the medium Gleason group. However, in PC spots with high Gleason grade, membrane localization is lost and a granular cytoplasmic localization with low intensity is observed (Fig. 3). The main difference of this marker among the groups is found in its location. For comparison, E-cadherin (a validated epithelial marker) expression and distribution was evaluated in PC TMA samples. This epithelial marker shows an expected membrane location in most samples with intensities varying from moderate to strong. In BPH spots, E-cadherin shows mainly baso-lateral location in gland epithelial cells and was absent in apical membrane. On the other hand, low Gleason grade samples show syndecan 1 intensity and distribution similar to BPH. However, in high Gleason grade spots, a loss of intensity associated to gland architecture disorganization is observed (Fig. 3E). In addition, E-cadherin distribution shows a mixed pattern including cytoplasm location (Fig. 3F). Significant decrease in E-cadherin expression is observed only in medium and high Gleason grade samples (Fig. 3F).

Bottom Line: Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells.Interestingly, syndecan 2 shows no changes associated to histological grade.It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1.

View Article: PubMed Central - PubMed

Affiliation: Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.

ABSTRACT
Prostate cancer (PC) is a leading male oncologic malignancy wideworld. During malignant transformation, normal epithelial cells undergo genetic and morphological changes known as epithelial-mesenchymal transition (EMT). Several regulatory genes and specific marker proteins are involved in PC EMT. Recently, syndecans have been associated with malignancy grade and Gleason score in PC. Considering that SNAIL is mainly a gene repressor increased in PC and that syndecan promoters have putative binding sites for this repressor, we propose that SNAIL might regulate syndecan expression during PC EMT. The aim of this study was to analyze immunochemically the expression of SNAIL, syndecans 1 and 2 and other EMT markers in a tissue microarray (TMA) of PC samples and PC cell lines. The TMAs included PC samples of different Gleason grade and benign prostatic hyperplasia (BPH) samples, as non‑malignant controls. PC3 and LNCaP cell lines were used as models of PC representing different tumorigenic capacities. Semi-quantitative immunohistochemistry was performed on TMAs and fluorescence immunocytochemistry and western blot analysis were conducted on cell cultures. Results show that SNAIL exhibits increased expression in high Gleason specimens compared to low histological grade and BPH samples. Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells. Conversely, syndecan 1, similarly to E-cadherin (a known marker of EMT), shows a decreased expression in high Gleason grades samples and PC3 cells. Interestingly, syndecan 2 shows no changes associated to histological grade. It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1. The mechanism by which SNAIL regulates the expression of syndecan 1 remains to be investigated.

Show MeSH
Related in: MedlinePlus