Insulin-like growth factor binding protein-1 inhibits cancer cell invasion and is associated with poor prognosis in hepatocellular carcinoma

Int J Clin Exp Pathol. 2014 Aug 15;7(9):5645-54. eCollection 2014.

Abstract

Insulin-like growth factor binding protein-1 (IGFBP-1) plays an important role in the development and progression of cancer. However, the expression of IGFBP-1 remains equivocal, and little is known about its clinicopathological significance and prognostic value in hepatocellular carcinoma (HCC). In this study, we evaluated the expression of IGFBP-1 in 90 paired HCC tissues and adjacent non-cancerous liver tissues and analyzed its clinical and prognostic significance. The results showed that IGFBP-1 was detected in cytoplasm as well as cell nucleus, and down-regulated in HCC tissues compared to the adjacent non-cancerous liver tissues. The decreased expression of IGFBP-1 was correlated with tumor differentiation, liver cirrhosis, microvascular invasion or metastasis, TNM stage and poor survival. Moreover, low levels of IGFBP-1 may be an independent prognostic indicator for the survival of patients with HCC. We also evaluated its function by adding recombinant IGFBP-1 to the cultured HCC cell lines HepG2 and MHCC97-H. The result of the invasion chamber assay showed that IGFBP-1 could inhibit the invasion of HepG2 and MHCC97-H. MMP-9 secretion by these cells was significantly decreased when the cells were treated with IGFBP-1. Our results suggest that IGFBP-1 inhibits the invasion and metastasis of HCC cells and that IGFBP-1 may be useful as a valuable marker for the prognosis of patients with HCC.

Keywords: IGFBP-1; MMP-9; hepatocellular carcinoma; invasion; poor prognosis; tumor suppressor gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy
  • Cell Movement* / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Insulin-Like Growth Factor Binding Protein 1 / genetics
  • Insulin-Like Growth Factor Binding Protein 1 / metabolism*
  • Insulin-Like Growth Factor Binding Protein 1 / pharmacology
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology
  • Risk Factors
  • Signal Transduction
  • Time Factors

Substances

  • Biomarkers, Tumor
  • IGFBP1 protein, human
  • Insulin-Like Growth Factor Binding Protein 1
  • RNA, Messenger
  • Recombinant Proteins
  • MMP9 protein, human
  • Matrix Metalloproteinase 9