title: Keratinocytes and head and neck squamous cell carcinoma cells regulate urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in fibroblasts.
abstract: BACKGROUND
  To investigate possible differences in the effects of soluble factors from oral squamous cell carcinoma (SCC) cells (UT-SCC-87) and normal oral keratinocytes (NOK) on fibroblast expression of genes involved in tumor stroma turnover.
  
  
  METHODS
  Transwell co-cultures with fibroblasts in collagen gels, and SCC cells or NOK in inserts were carried out. Fibroblast gene expression was measured with real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  The expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) was up-regulated in co-cultures with SCC cells but not with NOK. In contrast, both SCC cells and NOK regulated matrix metalloproteinase-1 (MMP1) and -3, and tissue inhibitor of metalloproteinases-2 (TIMP2) and -3 to a similar extent, while MMP2 and TIMP1 were largely unaffected. Interleukin 1 alpha (IL1α) up-regulated both MMP1 and MMP3 and down-regulated PAI-1, TIMP2 and -3.
  
  
  CONCLUSIONS
  SCC and NOK regulate fibroblast expression of genes involved in tumor stroma turnover differentially in vitro. These observations may contribute to a better understanding of the mechanisms behind extracellular matrix turnover in tumors.
authors.affiliation: Department of Surgical Sciences, Plastic Surgery, Uppsala University, 751 85 Uppsala, Sweden. malin.hakelius@akademiska.se
authors.forename: Malin
authors.initials: M
authors.lastname: Hakelius
authors.forename: Anita
authors.initials: A
authors.lastname: Koskela
authors.forename: Mikael
authors.initials: M
authors.lastname: Ivarsson
authors.forename: Reidar
authors.initials: R
authors.lastname: Grenman
authors.forename: Kristofer
authors.initials: K
authors.lastname: Rubin
authors.forename: Bengt
authors.initials: B
authors.lastname: Gerdin
authors.forename: Daniel
authors.initials: D
authors.lastname: Nowinski
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator
keywords: Head and neck cancer; PAI-1; differential regulation; keratinocytes; uPA