title: Normal Oral Keratinocytes and Head and Neck Squamous Carcinoma Cells Induce an Innate Response of Fibroblasts.
abstract: BACKGROUND
  Tumor stroma is similar to the connective tissue of chronic inflammation. The extracellular matrix of tumors is formed by cancer-associated fibroblasts that also modulate the inflammatory response.
  
  
  METHODS
  We studied the ability of oral keratinocytes (NOK) and oral squamous cell carcinoma cells (SCC) to induce an innate immune response in fibroblasts. Co-cultures with fibroblasts in collagen gels and keratinocytes in inserts were used. Pentraxin 3 (PTX3) was used as an indicator of an innate immune response.
  
  
  RESULTS
  SCC and NOK up-regulated fibroblast mRNA expression and protein release of PTX3. mRNA levels were more pronounced in cultures with malignant cells. The induction of PTX3 was abrogated by an interleukin-1 receptor antagonist
  
  
  CONCLUSIONS
  Keratinocytes have the capacity to induce an interleukin-1-dependent innate immune response by fibroblasts in vitro. This could be important for subsequent fibroblast modulation of the inflammatory reaction in non-malignant and malignant disease processes.
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 Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Vahid
authors.initials: V
authors.lastname: Reyhani
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: D002097:C-Reactive Protein / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D053582:Interleukin-1alpha / Q000096:biosynthesis; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology*; D009055:Mouth / Q000166:cytology* / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis; D000683:Serum Amyloid P-Component / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D053582:Interleukin-1alpha; D017472:Receptors, Interleukin-1; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
keywords: Co-culture; innate response; interleukin-1 alpha; pentraxin 3; tumor stroma