			Home About us Contact

Mesenchymal Markers (mesenchymal + marker)

Distribution by Scientific Domains

Medical Sciences	60%

Selected Abstracts

Blocking Wnt/LRP5 signaling by a soluble receptor modulates the epithelial to mesenchymal transition and suppresses met and metalloproteinases in osteosarcoma Saos-2 cells

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2007
Yi Guo
Abstract We previously reported the Wnt receptor low-density lipoprotein receptor-related protein 5 (LRP5) was frequently expressed in osteosarcoma (OS) tissue and correlated with metastasis and a lower disease-free survival. Subsequent in vitro analysis revealed that dominant-negative, soluble LRP5 (sLRP5) can reduce in vitro cellular invasion. In the current study, we examined the molecular mechanisms of blocking canonical Wnt signaling by sLRP5 in Saos-2 osteosarcoma cells. Transfection of sLRP5 caused a marked up-regulation of E-cadherin in this cell line. This increase in E-cadherin, seen primarily at the cell,cell contact borders, was associated with down-regulation of Slug and Twist, transcriptional repressors which mediate cancer invasion and metastasis. In contrast, N-cadherin, a mesenchymal marker, was reduced by sLRP5. In addition, blocking Wnt signaling by sLRP5 modulated other epithelial and mesenchymal markers (keratin 8 and 18, fibronectin), suggesting a reversal of epithelial,mesenchymal transition (EMT) seen during cancer progression. SLRP5 also reduced the expression of matrix metalloproteinase (MMP) 2 and 14, consistent with a decrease in invasive capacity. SLRP5 transfection decreased both Met expression and hepatocyte growth factor (HGF)-induced cell motility. Taken together, these results support a role for Wnt/LRP5 signaling in invasiveness of a subset of OS cells. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:964,971, 2007 [source]

Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells

INTERNATIONAL JOURNAL OF CANCER, Issue 12 2008
Atsushi Kanno
Abstract Periostin is a secretory protein that has been suggested to function as a cell adhesion molecule and promote the invasiveness or growth rate of tumors. However, little is known about the association of its expression and epithelial to mesenchymal transition (EMT), which is considered to play a crucial role in cancer cell metastasis. Thus, the authors investigated whether periostin could be involved in the process of EMT and the role of this gene in pancreatic cancer development. The expression of periostin was observed mainly in stromal cells but very little in cancer cells by immunohistochemistry and real-time RT-PCR. In vitro, pancreatic stellate cells (PSCs) exhibited a much higher basal expression of periostin compared with cancer cells. Periostin secreted in the supernatant from 293T cells that expressed periostin (approximately 150 ng/ml) inhibited the migration of pancreatic cancer cells. Coculture assay revealed that periostin expression in PSC was induced by pancreatic cancer cells. To assess the direct role of periostin in pancreatic cancer cells, the authors generated pancreatic cancer cell lines that stably express periostin. The induced expression of periostin (to 150 ng/ml) altered the morphology of cancer cells, changing them from mesenchymal to epithelial phenotypes with the induction of epithelial markers and a reduction of mesenchymal markers, and showed reduced cell migration in vitro and formed smaller tumors as well as suppressed metastasis in vivo. On the other hand, high concentration of recombinant periostin (1 ,g/ml) promoted cell migration with AKT activation. The findings suggest that periostin has biphasic effect on the development of pancreatic cancer. © 2008 Wiley-Liss, Inc. [source]

Blocking Wnt/LRP5 signaling by a soluble receptor modulates the epithelial to mesenchymal transition and suppresses met and metalloproteinases in osteosarcoma Saos-2 cells

Review Article: Review: Endothelial-myofibroblast transition, a new player in diabetic renal fibrosis

NEPHROLOGY, Issue 5 2010
JINHUA LI
ABSTRACT Diabetic nephropathy (DN) is the most common cause of chronic kidney failure and end-stage renal disease in the Western world. Studies from diabetic animal models and clinical trials have shown that inhibition of the renin-angiotensin system delays the progression of advanced DN. However, a recent large-scale clinical trial has revealed that inhibition of renin-angiotensin system in early phases of DN does not slow the decline of renal function or the development of morphological lesions, suggesting that different mechanism(s) may be involved in the different stages of DN. The role of epithelial-mesenchymal transition in renal fibrosis has been intensively investigated. Recently, endothelial-mesenchymal transition, or endothelial-myofibroblast transition (EndoMT) has emerged as another mechanism involved in both developmental and pathological processes. The essential role of EndoMT in cardiac development has been thoroughly studied. EndoMT also exists and contributes to the development and progression of cardiac fibrosis, lung fibrosis, liver fibrosis and corneal fibrosis. EndoMT is a specific form of epithelial-mesenchymal transition. During EndoMT, endothelial cells lose endothelial markers and obtain mesenchymal markers. Recent evidence from our laboratory and others suggests that EndoMT plays an important role in the development of renal fibrosis in several pathological settings, including experimental DN. This review considers the evidence supporting the occurrence of EndoMT in normal development and in pathology, as well as the latest findings suggesting EndoMT contributes to fibrosis in DN. Whether experimental findings of EndoMT will be reproduced in human studies remains to be determined. [source]

Posttransplant Bronchiolitis Obliterans Syndrome Is Associated with Bronchial Epithelial to Mesenchymal Transition

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009
S. Hodge
Bronchiolitis obliterans syndrome (BOS) compromises lung transplant outcomes and is characterised by airway epithelial damage and fibrosis. The process whereby the normal epithelial configuration is replaced by fibroblastic scar tissue is poorly understood, but recent studies have implicated epithelial mesenchymal transition (EMT). The primary aim of this study was to assess the utility of flow cytometry in detecting and quantifying EMT in bronchial epithelial cells. Large airway brushings were obtained at 33 bronchoscopies in 16 BOS-free and 6 BOS grade 1,3 patients at 2,120 months posttransplant. Flow cytometry was used to assess expression of the mesenchymal markers ,SMA, S100A4 and ED-A FN and HLA-DR. TGF ,1 and HGF were measured in Bronchoalveolar lavage (BAL). Expression of all three mesenchymal markers was increased in BOS, as was HLA-DR. BAL HGF, but not TGF ,1 was increased in BOS. Longitudinal investigation of one patient revealed a 100% increase in EMT markers concurrent with a 6-fold increase in BAL TGF ,1 and the diagnosis of BOS at 17 months posttransplant. Flow cytometric evaluation of bronchial epithelium may provide a novel and rapid means to assess lung allografts at risk of BOS. [source]