Home  About us  Contact
 

Mesenchymal Phenotype (mesenchymal + phenotype)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Tamoxifen resistance in MCF7 cells promotes EMT-like behaviour and involves modulation of ,-catenin phosphorylation

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2006
Stephen Hiscox
Abstract We have previously demonstrated that, following acquisition of endocrine resistance, breast cancer cells display an altered growth rate together with increased aggressive behaviour in vitro. Since dysfunctional cell,cell adhesive interactions can promote an aggressive phenotype, we investigated the integrity of this protein complex in our breast cancer model of tamoxifen resistance. In culture, tamoxifen-resistant MCF7 (TamR) cells grew as loosely packed colonies with loss of cell,cell junctions and demonstrated altered morphology characteristic of cells undergoing epithelial-to-mesenchymal transition (EMT). Neutralising E-cadherin function promoted the invasion and inhibited the aggregation of endocrine-sensitive MCF7 cells, whilst having little effect on the behaviour of TamR cells. Additionally, TamR cells had increased levels of tyrosine-phosphorylated ,-catenin, whilst serine/threonine-phosphorylated ,-catenin was decreased. These cells also displayed loss of association between ,-catenin and E-cadherin, increased cytoplasmic and nuclear ,-catenin and elevated transcription of ,-catenin target genes known to be involved in tumour progression and EMT. Inhibition of EGFR kinase activity in TamR cells reduced ,-catenin tyrosine phosphorylation, increased ,-catenin,E-cadherin association and promoted cell,cell adhesion. In such treated cells, the association of ,-catenin with Lef-1 and the transcription of c-myc, cyclin-D1, CD44 and COX-2 were also reduced. These results suggest that homotypic adhesion in tamoxifen-resistant breast cancer cells is dysfunctional due to EGFR-driven modulation of the phosphorylation status of ,-catenin and may contribute to an enhanced aggressive phenotype and transition towards a mesenchymal phenotype in vitro. © 2005 Wiley-Liss, Inc. [source]

Human islet-derived precursor cells can cycle between epithelial clusters and mesenchymal phenotypes

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009
Behrous Davani
Abstract We showed previously that undifferentiated, proliferating human islet-derived precursor cells (hIPCs) are a type of mesenchymal stem/stromal cell (MSC) that can be induced by serum deprivation to form clusters and ultimately differentiate in vitro to endocrine cells. We also demonstrated that partially differentiated hIPC clusters, when implanted under the kidney capsules of mice, continued to differentiate in vivo into hormone-producing cells. However, we noted that not all hIPC preparations yielded insulin-secreting cells in vivo and that in some animals no hormone-expressing cells were found. This suggested that the implanted cells were not always irreversibly committed to further differentiation and may even de-differentiate to a mesenchymal phenotype. In this study, we show that human cells with a mesenchymal phenotype are indeed found in the grafts of mice implanted with hIPCs in epithelial cell clusters (ECCs), which are obtained after 4-day in vitro culture of hIPCs in serum-free medium (SFM); mesenchymal cells were predominant in some grafts. We could mimic the transition of ECCs to de-differentiated mesenchymal cells in vitro by exposure to foetal bovine serum (FBS) or mouse serums, and to a significantly lesser extent to human serum. In a complementary series of experiments, we show that mouse serum and FBS are more effective stimulants of mesenchymal hIPC migration than is human serum. We found that proliferation was not needed for the transition from ECCs to de-differentiated cells because mitomycin-treated hIPCs that could not proliferate underwent a similar transition. Lastly, we show that cells exhibiting a mesenchymal phenotype can be found in grafts of adult human islets in mice. We conclude that epithelial-to-mesenchymal transition (EMT) of cells in hIPC ECCs can occur following implantation in mice. This potential for EMT of human islets or differentiated precursor cells must be considered in strategies for cell replacement therapy for diabetes. [source]

REVIEW ARTICLE: RCAS1, MT, and Vimentin as Potential Markers of Tumor Microenvironment Remodeling

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010
Magdalena Dutsch-Wicherek
Citation Dutsch-Wicherek M. RCAS1, MT, and vimentin as potential markers of tumor microenvironment remodeling. Am J Reprod Immunol 2010; 63: 181,188 A tumor stimulates the remodeling of its microenvironment for its own survival. To protect its own growth and induce angiogenesis, the tumor changes the structure of extracellular matrix and the function of existing cells; it thus chemo-attracts immune system cells altering their function. In our study, we discuss the potential markers of tumor microenvironment remodeling. For instance, RCAS1 is a protein responsible for tumor escape from host immunologic surveillance that additionally seems to be involved in the remodeling of the microenvironment. Another protein, metallothionein, which is both anti-apoptotic and pro-proliferative, is also responsible for modulating the response of immune system cells. Most likely, the expression of this protein by the fibroblasts of tumor microenvironment is related to the remodeled phenotype of these cells because of the tumor influence on cancer-associated fibroblasts. Lastly, vimentin is a protein that would appear to be the marker for the mesenchymal transition of cells from the epithelial phenotype. These cells seem to acquire the mesenchymal phenotype to migrate so that they can facilitate the development of metastases. Interestingly, the expression of vimentin has also been observed in the tumor microenvironment as well and may serve as a marker of a remodeled stroma in the process of facilitating tumor spread. [source]

Human islet-derived precursor cells can cycle between epithelial clusters and mesenchymal phenotypes

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009
Behrous Davani
Abstract We showed previously that undifferentiated, proliferating human islet-derived precursor cells (hIPCs) are a type of mesenchymal stem/stromal cell (MSC) that can be induced by serum deprivation to form clusters and ultimately differentiate in vitro to endocrine cells. We also demonstrated that partially differentiated hIPC clusters, when implanted under the kidney capsules of mice, continued to differentiate in vivo into hormone-producing cells. However, we noted that not all hIPC preparations yielded insulin-secreting cells in vivo and that in some animals no hormone-expressing cells were found. This suggested that the implanted cells were not always irreversibly committed to further differentiation and may even de-differentiate to a mesenchymal phenotype. In this study, we show that human cells with a mesenchymal phenotype are indeed found in the grafts of mice implanted with hIPCs in epithelial cell clusters (ECCs), which are obtained after 4-day in vitro culture of hIPCs in serum-free medium (SFM); mesenchymal cells were predominant in some grafts. We could mimic the transition of ECCs to de-differentiated mesenchymal cells in vitro by exposure to foetal bovine serum (FBS) or mouse serums, and to a significantly lesser extent to human serum. In a complementary series of experiments, we show that mouse serum and FBS are more effective stimulants of mesenchymal hIPC migration than is human serum. We found that proliferation was not needed for the transition from ECCs to de-differentiated cells because mitomycin-treated hIPCs that could not proliferate underwent a similar transition. Lastly, we show that cells exhibiting a mesenchymal phenotype can be found in grafts of adult human islets in mice. We conclude that epithelial-to-mesenchymal transition (EMT) of cells in hIPC ECCs can occur following implantation in mice. This potential for EMT of human islets or differentiated precursor cells must be considered in strategies for cell replacement therapy for diabetes. [source]

Signaling networks guiding epithelial,mesenchymal transitions during embryogenesis and cancer progression

CANCER SCIENCE, Issue 10 2007
Aristidis Moustakas
Epithelial,mesenchymal transition (EMT) describes the differentiation switch between polarized epithelial cells and contractile and motile mesenchymal cells, and facilitates cell movements and generation of new tissue types during embryogenesis. Many secreted polypeptides are implicated in the EMT process and their corresponding intracellular transduction pathways form highly interconnected networks. Transforming growth factor-,, Wnt, Notch and growth factors acting through tyrosine kinase receptors induce EMT and often act in a sequential manner. Such growth factors orchestrate the concerted regulation of an elaborate gene program and a complex protein network, needed for establishment of new mesenchymal phenotypes after disassembly of the main elements of epithelial architecture, such as desmosomes, as well as tight, adherens and gap junctions. EMT of tumor cells occurs during cancer progression and possibly generates cell types of the tumor stroma, such as cancer-associated myofibroblasts. EMT contributes to new tumor cell properties required for invasiveness and vascular intravasation during metastasis. Here we present some of the current mechanisms that mediate the process of EMT and discuss their relevance to cancer progression. (Cancer Sci 2007; 98: 1512,1520) [source]