title: EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression.
abstract: BACKGROUND
  An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC) progression.
  
  
  METHODS
  Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat.
  
  
  RESULTS
  OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner.
  
  
  CONCLUSIONS
  Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Lescaille
authors.forename: Suzanne
authors.initials: S
authors.lastname: Menashi
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Cavelier-Balloy
authors.forename: Farah
authors.initials: F
authors.lastname: Khayati
authors.forename: Cathy
authors.initials: C
authors.lastname: Quemener
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Podgorniak
authors.forename: Benyoussef
authors.initials: B
authors.lastname: Naïmi
authors.forename: Fabien
authors.initials: F
authors.lastname: Calvo
authors.forename: Céleste
authors.initials: C
authors.lastname: Lebbe
authors.forename: Samia
authors.initials: S
authors.lastname: Mourah
mesh_terms: D051926:Basigin / Q000502:physiology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000502:physiology*; D011230:Precancerous Conditions / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D051926:Basigin; D014568:Urokinase-Type Plasminogen Activator