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Åke Borg

Åke Borg

Principal investigator

Åke Borg

Endothelial Induced EMT in Breast Epithelial Cells with Stem Cell Properties

Author

  • Valgardur Sigurdsson
  • Bylgja Hilmarsdottir
  • Hekla Sigmundsdottir
  • Agla J. R. Fridriksdottir
  • Markus Ringnér
  • Rene Villadsen
  • Åke Borg
  • Bjarni A. Agnarsson
  • Ole William Petersen
  • Magnus K. Magnusson
  • Thorarinn Gudjonsson

Summary, in English

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.

Department/s

  • Breastcancer-genetics
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2011

Language

English

Publication/Series

PLoS ONE

Volume

6

Issue

9

Document type

Journal article

Publisher

Public Library of Science (PLoS)

Topic

  • Cancer and Oncology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1932-6203