Endothelial induced EMT in breast epithelial cells with stem cell properties.

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 endothelia...

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Autores principales: Valgardur Sigurdsson, Bylgja Hilmarsdottir, Hekla Sigmundsdottir, Agla J R Fridriksdottir, Markus Ringnér, Rene Villadsen, Ake Borg, Bjarni A Agnarsson, Ole William Petersen, Magnus K Magnusson, Thorarinn Gudjonsson
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:7a12b912dae542059f3c0643674c9ce52021-11-18T06:46:40ZEndothelial induced EMT in breast epithelial cells with stem cell properties.1932-620310.1371/journal.pone.0023833https://doaj.org/article/7a12b912dae542059f3c0643674c9ce52011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21915264/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Epithelial 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.Valgardur SigurdssonBylgja HilmarsdottirHekla SigmundsdottirAgla J R FridriksdottirMarkus RingnérRene VilladsenAke BorgBjarni A AgnarssonOle William PetersenMagnus K MagnussonThorarinn GudjonssonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e23833 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Valgardur Sigurdsson
Bylgja Hilmarsdottir
Hekla Sigmundsdottir
Agla J R Fridriksdottir
Markus Ringnér
Rene Villadsen
Ake Borg
Bjarni A Agnarsson
Ole William Petersen
Magnus K Magnusson
Thorarinn Gudjonsson
Endothelial induced EMT in breast epithelial cells with stem cell properties.
description 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.
format article
author Valgardur Sigurdsson
Bylgja Hilmarsdottir
Hekla Sigmundsdottir
Agla J R Fridriksdottir
Markus Ringnér
Rene Villadsen
Ake Borg
Bjarni A Agnarsson
Ole William Petersen
Magnus K Magnusson
Thorarinn Gudjonsson
author_facet Valgardur Sigurdsson
Bylgja Hilmarsdottir
Hekla Sigmundsdottir
Agla J R Fridriksdottir
Markus Ringnér
Rene Villadsen
Ake Borg
Bjarni A Agnarsson
Ole William Petersen
Magnus K Magnusson
Thorarinn Gudjonsson
author_sort Valgardur Sigurdsson
title Endothelial induced EMT in breast epithelial cells with stem cell properties.
title_short Endothelial induced EMT in breast epithelial cells with stem cell properties.
title_full Endothelial induced EMT in breast epithelial cells with stem cell properties.
title_fullStr Endothelial induced EMT in breast epithelial cells with stem cell properties.
title_full_unstemmed Endothelial induced EMT in breast epithelial cells with stem cell properties.
title_sort endothelial induced emt in breast epithelial cells with stem cell properties.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/7a12b912dae542059f3c0643674c9ce5
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