title: Characterization and clinical evaluation of CD10+ stroma cells in the breast cancer microenvironment.
abstract: OBJECTIVE
  There is growing evidence that interaction between stromal and tumor cells is pivotal in breast cancer progression and response to therapy. Based on earlier research suggesting that during breast cancer progression, striking changes occur in CD10(+) stromal cells, we aimed to better characterize this cell population and its clinical relevance.
  
  
  METHODS
  We developed a CD10(+) stroma gene expression signature (using HG U133 Plus 2.0) on the basis of the comparison of CD10 cells isolated from tumoral (n = 28) and normal (n = 3) breast tissue. We further characterized the CD10(+) cells by coculture experiments of representative breast cancer cell lines with the different CD10(+) stromal cell types (fibroblasts, myoepithelial, and mesenchymal stem cells). We then evaluated its clinical relevance in terms of in situ to invasive progression, invasive breast cancer prognosis, and prediction of efficacy of chemotherapy using publicly available data sets.
  
  
  RESULTS
  This 12-gene CD10(+) stroma signature includes, among others, genes involved in matrix remodeling (MMP11, MMP13, and COL10A1) and genes related to osteoblast differentiation (periostin). The coculture experiments showed that all 3 CD10(+) cell types contribute to the CD10(+) stroma signature, although mesenchymal stem cells have the highest CD10(+) stroma signature score. Of interest, this signature showed an important role in differentiating in situ from invasive breast cancer, in prognosis of the HER2(+) subpopulation of breast cancer only, and potentially in nonresponse to chemotherapy for those patients.
  
  
  CONCLUSIONS
  Our results highlight the importance of CD10(+) cells in breast cancer prognosis and efficacy of chemotherapy, particularly within the HER2(+) breast cancer disease.
authors.affiliation: Breast Cancer Translational Research Laboratory JC Heuson, Institut Jules Bordet, 125 Bld de Waterloo, Brussels 1000, Belgium. christine.desmedt@bordet.be
authors.forename: Christine
authors.initials: C
authors.lastname: Desmedt
authors.forename: Samira
authors.initials: S
authors.lastname: Majjaj
authors.forename: Naima
authors.initials: N
authors.lastname: Kheddoumi
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Singhal
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haibe-Kains
authors.forename: Frank
authors.initials: F
authors.lastname: El Ouriaghli
authors.forename: Carole
authors.initials: C
authors.lastname: Chaboteaux
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
authors.forename: Françoise
authors.initials: F
authors.lastname: Lallemand
authors.forename: Fabrice
authors.initials: F
authors.lastname: Journe
authors.forename: Hughes
authors.initials: H
authors.lastname: Duvillier
authors.forename: Sherene
authors.initials: S
authors.lastname: Loi
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
authors.forename: Sophie
authors.initials: S
authors.lastname: Dekoninck
authors.forename: Cédric
authors.initials: C
authors.lastname: Blanpain
authors.forename: Laurence
authors.initials: L
authors.lastname: Lagneaux
authors.forename: Nawal
authors.initials: N
authors.lastname: Houhou
authors.forename: Mauro
authors.initials: M
authors.lastname: Delorenzi
authors.forename: Denis
authors.initials: D
authors.lastname: Larsimont
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009367:Neoplasm Staging; D015260:Neprilysin / Q000378:metabolism*; D011379:Prognosis; D012372:ROC Curve; D017154:Stromal Cells / Q000378:metabolism; D016019:Survival Analysis; D059016:Tumor Microenvironment
chemical_list: D015260:Neprilysin