title: Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer.
abstract: BACKGROUND
  Breast cancer invasion and metastasis involves both epithelial and stromal changes. Our objective was to delineate the pivotal role stroma plays in invasion by comparing transcriptomes among stromal and epithelial cells in normal tissue and invasive breast cancer.
  
  
  METHODS
  Total RNA was isolated from epithelial and stromal cells that were laser captured from normal breast tissue (n = 5) and invasive breast cancer (n = 28). Gene expression was measured using Affymetrix U133A 2.0 GeneChips. Differential gene expression was evaluated and compared within a model that accounted for cell type (epithelial [E] versus stromal [S]), diagnosis (cancer [C] versus normal [N]) as well as cell type-diagnosis interactions.
  
  
  RESULTS
  Compared to NE, the CE transcriptome was highly enriched with genes in proliferative, motility and ECM ontologies. Differences in CS and NS transcriptomes suggested that the ECM was being remodeled in invasive breast cancer, as genes were over-represented in ECM and proteolytic ontologies. Genes more highly expressed in CS compared to CE were primarily ECM components or were involved in the remodeling of ECM, suggesting that ECM biosynthesis and remodeling were initiated in the tumor stroma.
  
  
  CONCLUSIONS
  Based on identified molecular cross-talk between the two contiguous cell populations, a mechanistic model that spurs invasion is proposed, that shows breast cancer invasion proceeds through the acquisition of a motile phenotype in tumor epithelial cells and a reactive phenotype in cancer associated fibroblasts.
authors: Animal Science, University of Vermont, Burlington, VT 05405, USA. ande1218@msu.edu
authors: Theresa
authors: T
authors: Casey
authors: Jeffrey
authors: J
authors: Bond
authors: Scott
authors: S
authors: Tighe
authors: Timothy
authors: T
authors: Hunter
authors: Laura
authors: L
authors: Lintault
authors: Osman
authors: O
authors: Patel
authors: Jonathan
authors: J
authors: Eneman
authors: Abigail
authors: A
authors: Crocker
authors: Jeffrey
authors: J
authors: White
authors: Joseph
authors: J
authors: Tessitore
authors: Mary
authors: M
authors: Stanley
authors: Seth
authors: S
authors: Harlow
authors: Donald
authors: D
authors: Weaver
authors: Hyman
authors: H
authors: Muss
authors: Karen
authors: K
authors: Plaut
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005109:Extracellular Matrix / Q000235:genetics; D005260:Female; D005347:Fibroblasts; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009367:Neoplasm Staging; D010641:Phenotype; D017154:Stromal Cells