title: VEGFR-1 activation-induced MMP-9-dependent invasion in hepatocellular carcinoma.
abstract: OBJECTIVE
  VEGFR-1 can promote invasion through epithelial-mesenchymal transition induction in hepatocellular carcinoma (HCC). This study aims to elucidate VEGFR-1 impact on proteolytic enzymes profile involved with invasion.
  
  
  METHODS
  The effect on cell invasion was evaluated by invasive and migration assays with and without VEGFR-1 activation. The mechanism was investigated by real-time PCR, western blot and gelatin zymography using inhibitors for MMP-9. In total, 95 HCC patients were enrolled for its clinical value evaluation.
  
  
  RESULTS
  VEGFR-1 activation induced invasion in HCC cells with an increase in the expression and activity of MMP-9 and Snail. MMP-9 blockage effectively inhibited VEGFR-1-induced invasion. High coexpression of both in HCC predicted a worse clinical outcome.
  
  
  CONCLUSIONS
  Data show a novel VEGFR-1 activation-to-MMP-9 mechanism promoting HCC invasion.
authors.affiliation: Department of Infectious diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Infectious diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Infectious diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Wanhua
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Infectious diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Infectious diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Chengyong
authors.initials: C
authors.lastname: Qin
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D040281:Vascular Endothelial Growth Factor Receptor-1; D020780:Matrix Metalloproteinase 9
keywords: MMP-9; Snail; VEGFR-1; hepatocellular carcinoma; invasion