2.50
Hdl Handle:
http://hdl.handle.net/2336/227555
Title:
Endothelial induced EMT in breast epithelial cells with stem cell properties.
Authors:
Sigurdsson, Valgardur; Hilmarsdottir, Bylgja; Sigmundsdottir, Hekla; Fridriksdottir, Agla J R; Ringnér, Markus; Villadsen, Rene; Borg, Ake; Agnarsson, Bjarni A; Petersen, Ole William; Magnusson, Magnus K; Gudjonsson, Thorarinn
Citation:
PLoS ONE 2011, 6(9):e23833
Issue Date:
2011
Abstract:
Epithelial to mesenchymal transition (EMT) is a critical event in cancer progression and is closely linked to the breast epithelial cancer stem cell phenotype. Given the close interaction between the vascular endothelium and cancer cells, especially at the invasive front, we asked whether endothelial cells might play a role in EMT. Using a 3D culture model we demonstrate that endothelial cells are potent inducers of EMT in D492 an immortalized breast epithelial cell line with stem cell properties. Endothelial induced mesenchymal-like cells (D492M) derived from D492, show reduced expression of keratins, a switch from E-Cadherin (E-Cad) to N-Cadherin (N-Cad) and enhanced migration. Acquisition of cancer stem cell associated characteristics like increased CD44(high)/CD24(low) ratio, resistance to apoptosis and anchorage independent growth was also seen in D492M cells. Endothelial induced EMT in D492 was partially blocked by inhibition of HGF signaling. Basal-like breast cancer, a vascular rich cancer with stem cell properties and adverse prognosis has been linked with EMT. We immunostained several basal-like breast cancer samples for endothelial and EMT markers. Cancer cells close to the vascular rich areas show no or decreased expression of E-Cad and increased N-Cad expression suggesting EMT. Collectively, we have shown in a 3D culture model that endothelial cells are potent inducers of EMT in breast epithelial cells with stem cell properties. Furthermore, we demonstrate that basal-like breast cancer contains cells with an EMT phenotype, most prominently close to vascular rich areas of these tumors. We conclude that endothelial cells are potent inducers of EMT and may play a role in progression of basal-like breast cancer.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.
Additional Links:
http://dx.doi.org/10.1371/journal.pone.0023833; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3167828/?tool=pubmed
Rights:
Archived with thanks to PloS one

Full metadata record

DC FieldValue Language
dc.contributor.authorSigurdsson, Valgarduren_GB
dc.contributor.authorHilmarsdottir, Bylgjaen_GB
dc.contributor.authorSigmundsdottir, Heklaen_GB
dc.contributor.authorFridriksdottir, Agla J Ren_GB
dc.contributor.authorRingnér, Markusen_GB
dc.contributor.authorVilladsen, Reneen_GB
dc.contributor.authorBorg, Akeen_GB
dc.contributor.authorAgnarsson, Bjarni Aen_GB
dc.contributor.authorPetersen, Ole Williamen_GB
dc.contributor.authorMagnusson, Magnus Ken_GB
dc.contributor.authorGudjonsson, Thorarinnen_GB
dc.date.accessioned2012-06-05T15:01:55Z-
dc.date.available2012-06-05T15:01:55Z-
dc.date.issued2011-
dc.date.submitted2012-06-05-
dc.identifier.citationPLoS ONE 2011, 6(9):e23833en_GB
dc.identifier.issn1932-6203-
dc.identifier.pmid21915264-
dc.identifier.doi10.1371/journal.pone.0023833-
dc.identifier.urihttp://hdl.handle.net/2336/227555-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractEpithelial to mesenchymal transition (EMT) is a critical event in cancer progression and is closely linked to the breast epithelial cancer stem cell phenotype. Given the close interaction between the vascular endothelium and cancer cells, especially at the invasive front, we asked whether endothelial cells might play a role in EMT. Using a 3D culture model we demonstrate that endothelial cells are potent inducers of EMT in D492 an immortalized breast epithelial cell line with stem cell properties. Endothelial induced mesenchymal-like cells (D492M) derived from D492, show reduced expression of keratins, a switch from E-Cadherin (E-Cad) to N-Cadherin (N-Cad) and enhanced migration. Acquisition of cancer stem cell associated characteristics like increased CD44(high)/CD24(low) ratio, resistance to apoptosis and anchorage independent growth was also seen in D492M cells. Endothelial induced EMT in D492 was partially blocked by inhibition of HGF signaling. Basal-like breast cancer, a vascular rich cancer with stem cell properties and adverse prognosis has been linked with EMT. We immunostained several basal-like breast cancer samples for endothelial and EMT markers. Cancer cells close to the vascular rich areas show no or decreased expression of E-Cad and increased N-Cad expression suggesting EMT. Collectively, we have shown in a 3D culture model that endothelial cells are potent inducers of EMT in breast epithelial cells with stem cell properties. Furthermore, we demonstrate that basal-like breast cancer contains cells with an EMT phenotype, most prominently close to vascular rich areas of these tumors. We conclude that endothelial cells are potent inducers of EMT and may play a role in progression of basal-like breast cancer.en_GB
dc.description.sponsorshipLandspitali University Hospital University of Iceland Science and Technology Policy Council European Science Foundationen_GB
dc.language.isoenen
dc.publisherPublic Library of Scienceen_GB
dc.relation.urlhttp://dx.doi.org/10.1371/journal.pone.0023833en_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3167828/?tool=pubmeden_GB
dc.rightsArchived with thanks to PloS oneen_GB
dc.subject.meshApoptosisen_GB
dc.subject.meshBlotting, Westernen_GB
dc.subject.meshCell Dedifferentiationen_GB
dc.subject.meshCell Lineen_GB
dc.subject.meshCell Line, Tumoren_GB
dc.subject.meshCells, Cultureden_GB
dc.subject.meshEpidermal Growth Factoren_GB
dc.subject.meshEpithelial Cellsen_GB
dc.subject.meshEpithelial-Mesenchymal Transitionen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFibroblast Growth Factorsen_GB
dc.subject.meshFlow Cytometryen_GB
dc.subject.meshHepatocyte Growth Factoren_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunochemistryen_GB
dc.subject.meshNeoplastic Stem Cellsen_GB
dc.subject.meshTransforming Growth Factor beta1en_GB
dc.titleEndothelial induced EMT in breast epithelial cells with stem cell properties.en
dc.typeArticleen
dc.contributor.departmentStem Cell Research Unit, Biomedical Center, School of Health Sciences, University of Iceland, Reykjavik, Iceland.en_GB
dc.identifier.journalPloS oneen_GB

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