title: Endothelial induced EMT in breast epithelial cells with stem cell properties.
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.
authors.affiliation: Stem Cell Research Unit, Biomedical Center, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Valgardur
authors.initials: V
authors.lastname: Sigurdsson
authors.forename: Bylgja
authors.initials: B
authors.lastname: Hilmarsdottir
authors.forename: Hekla
authors.initials: H
authors.lastname: Sigmundsdottir
authors.forename: Agla J R
authors.initials: AJ
authors.lastname: Fridriksdottir
authors.forename: Markus
authors.initials: M
authors.lastname: Ringnér
authors.forename: Rene
authors.initials: R
authors.lastname: Villadsen
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Bjarni A
authors.initials: BA
authors.lastname: Agnarsson
authors.forename: Ole William
authors.initials: OW
authors.lastname: Petersen
authors.forename: Magnus K
authors.initials: MK
authors.lastname: Magnusson
authors.forename: Thorarinn
authors.initials: T
authors.lastname: Gudjonsson
mesh_terms: D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D054337:Cell Dedifferentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005434:Flow Cytometry; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007120:Immunochemistry; D066298:In Vitro Techniques; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor