title: Mesenchymal precursor cells maintain the differentiation and proliferation potentials of breast epithelial cells.
abstract: BACKGROUND
  Stromal-epithelial interactions play a fundamental role in tissue homeostasis, controlling cell proliferation and differentiation. Not surprisingly, aberrant stromal-epithelial interactions contribute to malignancies. Studies of the cellular and molecular mechanisms underlying these interactions require ex vivo experimental model systems that recapitulate the complexity of human tissue without compromising the differentiation and proliferation potentials of human primary cells.
  
  
  METHODS
  We isolated and characterized human breast epithelial and mesenchymal precursors from reduction mammoplasty tissue and tagged them with lentiviral vectors. We assembled heterotypic co-cultures and compared mesenchymal and epithelial cells to cells in corresponding monocultures by analyzing growth, differentiation potentials, and gene expression profiles.
  
  
  RESULTS
  We show that heterotypic culture of non-immortalized human primary breast epithelial and mesenchymal precursors maintains their proliferation and differentiation potentials and constrains their growth. We further describe the gene expression profiles of stromal and epithelial cells in co-cultures and monocultures and show increased expression of the tumor growth factor beta (TGFβ) family member inhibin beta A (INHBA) in mesenchymal cells grown as co-cultures compared with monocultures. Notably, overexpression of INHBA in mesenchymal cells increases colony formation potential of epithelial cells, suggesting that it contributes to the dynamic reciprocity between breast mesenchymal and epithelial cells.
  
  
  CONCLUSIONS
  The described heterotypic co-culture system will prove useful for further characterization of the molecular mechanisms mediating interactions between human normal or neoplastic breast epithelial cells and the stroma, and will provide a framework to test the relevance of the ever-increasing number of oncogenomic alterations identified in human breast cancer.
authors.forename: Stephan
authors.initials: S
authors.lastname: Duss
authors.forename: Heike
authors.initials: H
authors.lastname: Brinkhaus
authors.forename: Adrian
authors.initials: A
authors.lastname: Britschgi
authors.forename: Erik
authors.initials: E
authors.lastname: Cabuy
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Frey
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Schaefer
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bentires-Alj
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000166:cytology; D001940:Breast / Q000166:cytology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D024161:Collagen Type XI / Q000096:biosynthesis; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D028322:Inhibin-beta Subunits / Q000096:biosynthesis / Q000378:metabolism*; D039001:Integrin alpha Chains / Q000096:biosynthesis; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011509:Proteoglycans / Q000096:biosynthesis; D015398:Signal Transduction; D000071232:Small Leucine-Rich Proteoglycans; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C574182:COL11A1 protein, human; D024161:Collagen Type XI; C119499:EPYC protein, human; C121535:ITGA11 protein, human; D039001:Integrin alpha Chains; D011509:Proteoglycans; D000071232:Small Leucine-Rich Proteoglycans; D016212:Transforming Growth Factor beta; C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13