title: Human breast cancer associated fibroblasts exhibit subtype specific gene expression profiles.
abstract: BACKGROUND
  Breast cancer is a heterogeneous disease for which prognosis and treatment strategies are largely governed by the receptor status (estrogen, progesterone and Her2) of the tumor cells. Gene expression profiling of whole breast tumors further stratifies breast cancer into several molecular subtypes which also co-segregate with the receptor status of the tumor cells. We postulated that cancer associated fibroblasts (CAFs) within the tumor stroma may exhibit subtype specific gene expression profiles and thus contribute to the biology of the disease in a subtype specific manner. Several studies have reported gene expression profile differences between CAFs and normal breast fibroblasts but in none of these studies were the results stratified based on tumor subtypes.
  
  
  METHODS
  To address whether gene expression in breast cancer associated fibroblasts varies between breast cancer subtypes, we compared the gene expression profiles of early passage primary CAFs isolated from twenty human breast cancer samples representing three main subtypes; seven ER+, seven triple negative (TNBC) and six Her2+.
  
  
  RESULTS
  We observed significant expression differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and ER + cancers, particularly in pathways associated with cytoskeleton and integrin signaling. In the case of Her2+ breast cancer, the signaling pathways found to be selectively up regulated in CAFs likely contribute to the enhanced migration of breast cancer cells in transwell assays and may contribute to the unfavorable prognosis of Her2+ breast cancer.
  
  
  CONCLUSIONS
  These data demonstrate that in addition to the distinct molecular profiles that characterize the neoplastic cells, CAF gene expression is also differentially regulated in distinct subtypes of breast cancer.
authors.affiliation: Department of Surgery, Division of Endocrine and Oncologic Surgery, Rena Rowan Breast Center, Abramson Cancer Center, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA 19104, USA. Julia.tchou@uphs.upenn.edu
authors.forename: Julia
authors.initials: J
authors.lastname: Tchou
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Kossenkov
authors.forename: Lisa
authors.initials: L
authors.lastname: Chang
authors.forename: Celine
authors.initials: C
authors.lastname: Satija
authors.forename: Meenhard
authors.initials: M
authors.lastname: Herlyn
authors.forename: Louise C
authors.initials: LC
authors.lastname: Showe
authors.forename: Ellen
authors.initials: E
authors.lastname: Puré
mesh_terms: D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D010641:Phenotype; D025341:Principal Component Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen