Molecular characterization of the tumor microenvironment in breast cancer.
Here we describe the comprehensive gene expression profiles of each cell type composing normal breast tissue and in situ and invasive breast carcinomas using serial analysis of gene expression. Based on these data, we determined that extensive gene expression changes occur in all cell types during cancer progression and that a significant fraction of altered genes encode secreted proteins and receptors. Despite the dramatic gene expression changes in all cell types, genetic alterations were detected only in cancer epithelial cells. The CXCL14 and CXCL12 chemokines overexpressed in tumor myoepithelial cells and myofibroblasts, respectively, bind to receptors on epithelial cells and enhance their proliferation, migration, and invasion. Thus, chemokines may play a role in breast tumorigenesis by acting as paracrine factors.
Allinen
Minna
M
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Beroukhim
Rameen
R
Cai
Li
L
Brennan
Cameron
C
Lahti-Domenici
Jaana
J
Huang
Haiyan
H
Porter
Dale
D
Hu
Min
M
Chin
Lynda
L
Richardson
Andrea
A
Schnitt
Stuart
S
Sellers
William R
WR
Polyak
Kornelia
K
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D006801:Humans; D009130:Muscle, Smooth / Q000166:cytology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; C118056:CXCL14 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D009363:Neoplasm Proteins