6382

SDC1

The epithelial-mesenchymal transition (EMT) is considered a key step in tumor progression, where the invasive cancer cells change from epithelial to mesenchymal phenotype. During this process, a decrease or loss in adhesion molecules expression and an increase in migration molecules expression are observed. The aim of this work was to determine the expression and cellular distribution of syndecan-1 and -2 (migration molecules) and E-cadherin and beta-catenin (adhesion molecules) in different stages of prostate cancer progression. A quantitative immunohistochemical study of these molecules was carried out in tissue samples from benign prostatic hyperplasia and prostate carcinoma, with low and high Gleason score, obtained from biopsies archives of the Clinic Hospital of the University of Chile and Dipreca Hospital. Polyclonal specific antibodies and amplification system of estreptavidin-biotin peroxidase and diaminobenzidine were used. Syndecan-1 was uniformly expressed in basolateral membranes of normal epithelium, changing to a granular cytoplasmatic expression pattern in carcinomas. Syndecan-2 was observed mainly in a cytoplasmatic granular pattern, with high immunostaining intensity in areas of low Gleason score. E-cadherin was detected in basolateral membrane of normal epithelia showing decreased expression in high Gleason score samples. beta-Catenin was found in cell membranes of normal epithelia changing its distribution toward the nucleus and cytoplasm in carcinoma samples. We concluded that changes in expression and cell distribution of E-cadherin and beta-catenin correlated with the progression degree of prostate adenocarcinoma, suggesting a role of these molecules as markers of progression and prognosis. Furthermore, changes in the pattern expression of syndecan-1 and -2 indicate that both molecules may be involved in the EMT and tumor progression of prostate cancer.CI - Copyright (c) 2010 Elsevier Inc. All rights reserved.

The epithelial-mesenchymal transition (EMT) of proximal tubular epithelial cells (PTECs) into myofibroblasts contributes to the establishment of fibrosis that leads to end stage renal disease. FGF-2 induces EMT in PTECs. Because the interaction between FGF-2 and its receptor is mediated by heparan sulfate (HS) and syndecans, we speculated that a deranged HS/syndecans regulation impairs FGF-2 activity. Heparanase is crucial for the correct turnover of HS/syndecans. The aim of the present study was to assess the role of heparanase on epithelial-mesenchymal transition induced by FGF-2 in renal tubular cells. In human kidney 2 (HK2) PTEC cultures, although FGF-2 induces EMT in the wild-type clone, it is ineffective in heparanase-silenced cells. The FGF-2 induced EMT is through a stable activation of PI3K/AKT which is only transient in heparanase-silenced cells. In PTECs, FGF-2 induces an autocrine loop which sustains its signal through multiple mechanisms (reduction in syndecan-1, increase in heparanase, and matrix metalloproteinase 9). Thus, heparanase is necessary for FGF-2 to produce EMT in PTECs and to sustain FGF-2 intracellular signaling. Heparanase contributes to a synergistic loop for handling syndecan-1, facilitating FGF-2 induced-EMT. In conclusion, heparanase plays a role in the tubular-interstitial compartment favoring the FGF-2-dependent EMT of tubular cells. Hence, heparanase is an interesting pharmacological target for the prevention of renal fibrosis.

MicroRNAs (miRNAs) are small noncoding RNAs with a length of approximately 19-24 nucleotides that regulate gene expression through translational inhibition and contribute to the progression of various tumors including prostate cancer. Aberrant expression of miRNAs has been implicated in the progression and metastasis of prostate cancer. The present study aimed to investigate whether miR-331-3p controlled by syndecan-1 positively affects the epithelial-to-mesenchymal transition (EMT). Overexpression of miR-331-3p upregulated mesenchymal markers such as vimentin, N-cadherin, and snail and downregulated epithelial markers such as E-cadherin and desmoplakin in the prostate cancer cell line PC3. We identified Neuropilin 2 and nucleus accumbens-associated protein 1 as putative target molecules in silico, as they were closely associated with the expression of miR-331-3p and TGF-beta/Smad 4 signals. In situ hybridization and immunohistochemistry of radical prostatectomy samples revealed miR-331-3p in cancer cells with high Gleason patterns, in which EMT was demonstrated by decreased E-cadherin, and increased vimentin staining. Syndecan-1 gene silencing decreased levels of Dicer, which is involved in miRNA maturation. MiR-331-3p-mediated miRNA maturation and enhanced EMT via effects on TGF-beta/Smad 4 and Dicer are essential for the development of prostate cancer mediated by syndecan-1. (c) 2015 Wiley Periodicals, Inc.CI - (c) 2015 Wiley Periodicals, Inc.

epithelial-mesenchymal transition (EMT) is one of the major processes that contribute to the occurrence of cancer metastasis. EMT has been associated with the development of oral cancer. Syndecan1 (SDC1) is a key cellsurface adhesion molecule and its expression level inversely correlates with tumor differentiation and prognosis. In the present study, we aimed to determine the role of SDC1 in oral cancer progression and investigate the molecular mechanisms through which SDC1 regulates the EMT and invasiveness of oral cancer cells. We demonstrated that basal SDC1 expression levels were lower in four oral cancer cell lines (KB, Tca8113, ACC2 and CAL27), than in normal human periodontal ligament fibroblasts. Ectopic overexpression of SDC1 resulted in morphological transformation, decreased expression of EMTassociated markers, as well as decreased migration, invasiveness and proliferation of oral cancer cells. In contrast, downregulation of the expression of SDC1 caused the opposite results. Furthermore, the knockdown of endogenous SDC1 activated the extracellular signalregulated kinase (ERK) cascade, upregulated the expression of Snail and inhibited the expression of Ecadherin. In conclusion, our findings revealed that SDC1 suppressed EMT via the modulation of the ERK signaling pathway that, in turn, negatively affected the invasiveness of human oral cancer cells. Our results provided useful evidence about the potential use of SDC1 as a molecular target for therapeutic interventions in human oral cancer.