title: Differential Gene Regulation in Fibroblasts in Co-culture with Keratinocytes and Head and Neck SCC Cells.
abstract: BACKGROUND
  While carcinoma-associated fibroblasts (CAFs) support tumorigenesis, normal tissue fibroblasts suppress tumor progression. Mechanisms behind conversion of fibroblasts into a CAF phenotype are largely unrevealed.
  
  
  METHODS
  Transwell co-cultures with fibroblasts in collagen gels and squamous-cell carcinoma (SCC) cells or normal oral keratinocytes (NOKs) in inserts. Differences in fibroblast global gene expression were analyzed using Affymetrix arrays and subsequent functional annotation and cluster analysis, as well as gene set enrichment analysis were performed.
  
  
  RESULTS
  There were 52 up-regulated and 30 down-regulated transcript IDs (>2-fold, p<0.05) in fibroblasts co-cultured with SCC compared to NOKs. Functional analysis demonstrated an enrichment of collagen-related genes. There were similarities with gene sets reflecting a non-specific, innate-type response with activation of both interferon pathways and connective tissue turnover.
  
  
  CONCLUSIONS
  There were distinct differences in fibroblast gene expression between the co-culture types. Many were in genes related to an innate-type of response and to connective tissue turnover.
authors.affiliation: Department of Surgical Sciences, Plastic Surgery, Uppsala University, Uppsala, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Hakelius
authors.affiliation: Department of Surgical Sciences, Plastic Surgery, Uppsala University, Uppsala, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Saiepour
authors.affiliation: Array Facility, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Göransson
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Kristofer
authors.initials: K
authors.lastname: Rubin
authors.affiliation: Department of Surgical Sciences, Plastic Surgery, Uppsala University, Uppsala, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Gerdin
authors.affiliation: Department of Surgical Sciences, Plastic Surgery, Uppsala University, Uppsala, Sweden daniel.nowinski@surgsci.uu.se.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nowinski
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018920:Coculture Techniques; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis
chemical_list: D009363:Neoplasm Proteins
keywords: Head and neck cancer; array; differential gene regulation; keratinocytes