title: Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas.
abstract: OBJECTIVE
  Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, play important roles in tumor development and progression. In this study, we measured the serum HGF levels in patients with esophageal squamous cell carcinoma (ESCC) to evaluate its relationships with clinicopathologic features and the role of HGF in ESCC.
  
  
  METHODS
  One hundred and forty-nine patients with ESCC were studied. Pretherapy serum was collected and ELISA was used to detect the concentrations of HGF, vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8). The function of HGF was shown by invasion chamber assay.
  
  
  RESULTS
  Pretherapy serum HGF was found to be significantly higher in patients with ESCC than in control subjects. The levels of HGF correlated significantly with advanced tumor metastasis stage and survival. Multivariate analyses showed that serum HGF level in cell migration was an independent prognostic factor. Increased HGF serum levels correlated positively with serum levels of VEGF and IL-8. Our results also showed that HGF was overexpressed in ESCC tissues and cell lines. In vitro study showed that HGF could stimulate ESCC cell to express VEGF and IL-8 and markedly enhance invasion and migration of ESCC cells. Furthermore, HGF-induced IL-8 and VEGF expression was dependent on extracellular signal-regulated kinase signaling pathways. The inhibition of extracellular signal-regulated kinase activation reduced HGF-mediated IL-8 and VEGF expression.
  
  
  CONCLUSIONS
  Our results suggest that serum HGF may be a useful biomarker of tumor progression and a valuable independent prognostic factor in patients with ESCC. HGF may be involved in the progression of ESCC as an autocrine/paracrine factor via enhancing angiogenesis and tumor cell invasion and migration.
authors.affiliation: Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong, PR China. slaw@hku.hk
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.forename: Brian
authors.initials: B
authors.lastname: Cao
authors.forename: Simon
authors.initials: S
authors.lastname: Law
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Ping Yin
authors.initials: PY
authors.lastname: Lee
authors.forename: Leo
authors.initials: L
authors.lastname: Cheung
authors.forename: Yongxong
authors.initials: Y
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Hiu Man
authors.initials: HM
authors.lastname: Chan
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.forename: John
authors.initials: J
authors.lastname: Luk
authors.forename: George
authors.initials: G
authors.lastname: Vande Woude
authors.forename: John
authors.initials: J
authors.lastname: Wong
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000175:diagnosis; D002465:Cell Movement / Q000502:physiology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000097:blood* / Q000175:diagnosis; D004947:Esophagus / Q000378:metabolism; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D016209:Interleukin-8 / Q000097:blood*; D020935:MAP Kinase Signaling System; D008297:Male; D009389:Neovascularization, Pathologic; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met