title: Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture.
abstract: BACKGROUND
  Epithelial-stromal interaction provides regulatory signals that maintain correct histoarchitecture and homeostasis in the normal breast and facilitates tumor progression in breast cancer. However, research on the regulatory role of the endothelial component in the normal and malignant breast gland has largely been neglected. The aim of the study was to investigate the effects of endothelial cells on growth and differentiation of human breast epithelial cells in a three-dimensional (3D) co-culture assay.
  
  
  METHODS
  Breast luminal and myoepithelial cells and endothelial cells were isolated from reduction mammoplasties. Primary cells and established normal and malignant breast cell lines were embedded in reconstituted basement membrane in direct co-culture with endothelial cells and by separation of Transwell filters. Morphogenic and phenotypic profiles of co-cultures was evaluated by phase contrast microscopy, immunostaining and confocal microscopy.
  
  
  RESULTS
  In co-culture, endothelial cells stimulate proliferation of both luminal- and myoepithelial cells. Furthermore, endothelial cells induce a subpopulation of luminal epithelial cells to form large acini/ducts with a large and clear lumen. Endothelial cells also stimulate growth and cloning efficiency of normal and malignant breast epithelial cell lines. Transwell and gradient co-culture studies show that endothelial derived effects are mediated - at least partially - by soluble factors.
  
  
  CONCLUSIONS
  Breast endothelial cells - beside their role in transporting nutrients and oxygen to tissues - are vital component of the epithelial microenvironment in the breast and provide proliferative signals to the normal and malignant breast epithelium. These growth promoting effects of endothelial cells should be taken into consideration in breast cancer biology.
authors.affiliation: Stem cell research unit, Department of anatomy, Faculty of medicine, University of Iceland and Department of laboratory hematology, Landspitali, university hospital, (Vatnsmýrarvegur 16), Reykjavík, (101), Iceland. tgudjons@hi.is.
authors.forename: Saevar
authors.initials: S
authors.lastname: Ingthorsson
authors.forename: Valgardur
authors.initials: V
authors.lastname: Sigurdsson
authors.forename: Agla
authors.initials: A
authors.lastname: Fridriksdottir
authors.forename: Jon G
authors.initials: JG
authors.lastname: Jonasson
authors.forename: Jens
authors.initials: J
authors.lastname: Kjartansson
authors.forename: Magnus K
authors.initials: MK
authors.lastname: Magnusson
authors.forename: Thorarinn
authors.initials: T
authors.lastname: Gudjonsson