serval:BIB_3AA4B56DD908
Characterization and clinical evaluation of CD10+ stroma cells in the breast cancer microenvironment.
10.1158/1078-0432.CCR-11-0383
000300628100011
22235100
Desmedt
C.
author
Majjaj
S.
author
Kheddoumi
N.
author
Singhal
S.K.
author
Haibe-Kains
B.
author
El Ouriaghli
F.
author
Chaboteaux
C.
author
Michiels
S.
author
Lallemand
F.
author
Journe
F.
author
Duvillier
H.
author
Loi
S.
author
Quackenbush
J.
author
Dekoninck
S.
author
Blanpain
C.
author
Lagneaux
L.
author
Houhou
N.
author
Delorenzi
M.
author
Larsimont
D.
author
Piccart
M.
author
Sotiriou
C.
author
article
2012
Clinical Cancer Research
1078-0432
1078-0432
journal
18
4
1004-1014
PURPOSE: 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.
EXPERIMENTAL DESIGN: 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.
eng
60_published
true
peer-reviewed
University of Lausanne
mailto:serval_help@unil.ch
http://www.unil.ch/serval
http://serval.unil.ch/disclaimer
https://serval.unil.ch/notice/serval:BIB_3AA4B56DD908