TY - JOUR
T1 - Endothelial induced EMT in breast epithelial cells with stem cell properties
AU - Sigurdsson, Valgardur
AU - Hilmarsdottir, Bylgja
AU - Sigmundsdottir, Hekla
AU - Fridriksdottir, Agla J R
AU - Ringnér, Markus
AU - Villadsen, Rene
AU - Borg, Ake
AU - Agnarsson, Bjarni A
AU - Petersen, Ole William
AU - Magnusson, Magnus K
AU - Gudjonsson, Thorarinn
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Blotting, Western
KW - Cell Dedifferentiation
KW - Cell Line
KW - Cell Line, Tumor
KW - Cells, Cultured
KW - Epidermal Growth Factor
KW - Epithelial Cells
KW - Epithelial-Mesenchymal Transition
KW - Female
KW - Fibroblast Growth Factors
KW - Flow Cytometry
KW - Hepatocyte Growth Factor
KW - Humans
KW - Immunochemistry
KW - Neoplastic Stem Cells
KW - Transforming Growth Factor beta1
U2 - 10.1371/journal.pone.0023833
DO - 10.1371/journal.pone.0023833
M3 - Journal article
C2 - 21915264
SN - 1932-6203
VL - 6
SP - e23833
JO - P L o S One
JF - P L o S One
IS - 9
ER -
