title: Normal mammary fibroblasts induce reversion of the malignant phenotype in human primary breast cancer.
abstract: OBJECTIVE
  The tumor microenvironment plays a major role in tumor growth and progression. Its manipulation can lead to a reversion of the malignant phenotype. Here we explored the ability of normal mammary fibroblasts (HMFs) to induce reversion of the malignant phenotype of primary breast carcinoma cells (PBCs) in a three-dimensional (3D) context.
  
  
  METHODS
  PBCs were isolated from 13 primary breast carcinomas and cultured in 3D collagen-I gels as mono- or co-culture with HMFs.
  
  
  RESULTS
  In five co-cultures, PBCs exhibited reversion of their malignant phenotype, whereas PBCs in matched monocultures exhibited disorganized growth. Reversion, defined as the restoration of the complete baso-apical polarity axis, was confirmed with established polarity markers. Secretion of the tissue-specific glycoprotein MAM-6 into the acinar lumens and deposition of basement membrane indicated functional differentiation. Gene expression analysis revealed a set of differentially regulated genes which possibly affect the reversion process. These included MAL, ELF5, MAP6, ZMYND11 and SQLE.
  
  
  CONCLUSIONS
  These findings highlight the significant role of fibroblasts in regulating the carcinoma phenotype.
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Römer
authors.forename: Inke
authors.initials: I
authors.lastname: Lühr
authors.forename: Andreas
authors.initials: A
authors.lastname: Klein
authors.forename: Andreas
authors.initials: A
authors.lastname: Friedl
authors.forename: Susanne
authors.initials: S
authors.lastname: Sebens
authors.forename: Frank
authors.initials: F
authors.lastname: Rösel
authors.forename: Norbert
authors.initials: N
authors.lastname: Arnold
authors.forename: Alexander
authors.initials: A
authors.lastname: Strauss
authors.forename: Walter
authors.initials: W
authors.lastname: Jonat
authors.forename: Maret
authors.initials: M
authors.lastname: Bauer
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001940:Breast / Q000166:cytology* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication; D018929:Cell Culture Techniques; D002471:Cell Transformation, Neoplastic; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor