title: Biological characteristics and genetic heterogeneity between carcinoma-associated fibroblasts and their paired normal fibroblasts in human breast cancer.
abstract: BACKGROUND
  The extensional signals in cross-talk between stromal cells and tumor cells generated from extracellular matrix molecules, soluble factor, and cell-cell adhesion complexes cooperate at the extra- and intracellular level in the tumor microenvironment. CAFs are the primary type of stromal cells in the tumor microenvironment and play a pivotal role in tumorigenesis and development. Hitherto, there is hardly any systematic analysis of the intrinsic relationship between CAFs function and its abnormal signaling pathway. The extreme complexity of CAFs' features and their role in tumor development are needed to be further investigated.
  
  
  RESULTS
  We primary cultured CAFs and NFs from early stages of breast cancer tissue and identified them using their biomarker by immunohistochemistry for Fibronectin, α-SMA and FAP. Microarray was applied to analyze gene expression profiles of human breast CAFs and the paired NFs. The Up-regulated genes classified by Gene Ontology, signal pathways enriched by DAVID pathway analysis. Abnormal signaling pathways in breast cancer CAFs are involved in cell cycle, cell adhesion, signal transduction and protein transport being reported in CAFs derived from other tumors. Significantly, the altered ATM signaling pathway, a set of cell cycle regulated signaling, and immune associated signaling are identified to be changed in CAFs.
  
  
  CONCLUSIONS
  CAFs have the vigorous ability of proliferation and potential of invasion and migration comparing with NFs. CAFs could promote breast cancer cell invasion under co-culture conditions through up-regulated CCL18 and CXCL12. Consistently with its biologic behavior, the gene expression profiling analyzed by microarray shows that some of key signaling pathways, such as cell cycle, cell adhesion, and secreting factors play an important role in CAFs. The altered ATM signaling pathway is abnormally active in the early stage of breast cancer. The set of immune associated signaling may be involved in tumor cell immune evasion.
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Qiongle
authors.initials: Q
authors.lastname: Peng
authors.forename: Liuyang
authors.initials: L
authors.lastname: Zhao
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Hou
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Liyang
authors.initials: L
authors.lastname: Wang
authors.forename: Haojun
authors.initials: H
authors.lastname: Luo
authors.forename: Huimin
authors.initials: H
authors.lastname: Peng
authors.forename: Manran
authors.initials: M
authors.lastname: Liu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002469:Cell Separation; D019742:Chemokines, CC / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D018740:Genetic Heterogeneity; D006801:Humans; D009361:Neoplasm Invasiveness; D059467:Transcriptome / Q000235:genetics; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: C111792:CCL18 protein, human; D019742:Chemokines, CC