Tumor-derived hepatocyte growth factor is associated with poor prognosis of patients with glioma and influences the chemosensitivity of glioma cell line to cisplatin in vitro

World J Surg Oncol. 2012 Jun 28:10:128. doi: 10.1186/1477-7819-10-128.

Abstract

Background: We examined the association of tumor-derived hepatocyte growth factor (HGF) with the clinicopathological features of gliomas and investigated the effect of HGF inhibition on the biological behavior of tumor cells in vitro in order to determine whether HGF is a valuable prognostic predictor for glioma patients.

Methods: Seventy-six cases of glioma were collected. The tumor-derived HGF expression, cell proliferation index (PI) and intratumoral microvessels were evaluated by immunohistochemistry. Correlation between immunostaining and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. U87MG glioma cells were transfected with short interference (si)-RNA for HGF, and the cell viability, migratory ability and chemosensitivity to cisplatin were evaluated in vitro.

Results: Both high HGF expression in tumor cells (59.2%, 45/76) and high PI were significantly associated with high-grade glioma and increased microvessels in tumors (P < 0.05). However, only histological grading (P = 0.004) and high-expression of HGF (P = 0.008) emerged as independent prognostic factors for the overall survival of glioma patients. The tumor-derived HGF mRNA and protein expressions were significantly decreased in vitro after transfection of HGF siRNA. HGF siRNA inhibited the cell growth and reduced cell migratory ability. Moreover, HGF siRNA transfection enhanced the chemosensitivity of U87MG glioma cells to cisplatin.

Conclusion: This study indicated that there was significant correlation among tumor cell-derived HGF, cell proliferation and microvessel proliferation in gliomas. HGF might influence tumor progression by modulating the cell growth, migration and chemoresistance to drugs. Increased expression of HGF may be a valuable predictor for prognostic evaluation of glioma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Cell Line, Tumor / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation
  • Cell Survival / drug effects
  • Child
  • Cisplatin / pharmacology*
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm*
  • Female
  • Follow-Up Studies
  • Glioma / drug therapy
  • Glioma / metabolism*
  • Glioma / mortality
  • Glioma / pathology
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / metabolism
  • Polymerase Chain Reaction
  • Prognosis
  • Survival Analysis
  • Young Adult

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • HGF protein, human
  • Hepatocyte Growth Factor
  • Cisplatin