Correlation of Delta-like ligand 4 (DLL4) with VEGF and HIF-1α expression in human glioma

Asian Pac J Cancer Prev. 2011;12(1):215-8.

Abstract

To investigate the potential role of the notch ligand delta-like ligand 4 (DLL4) in glioma angiogenesis, we examined whether its expression correlates with that of vascular endothelial growth factor (VEGF) and hypoxia-induced factor-1α (HIF-1α). Eighty-two specimens of human glioma and 7 of normal brain tissue were subjected to immunohistochemical analysis for DLL4, VEGF and HIF-1α expression. Statistical analysis were performed to determine if protein expression correlated with clinicopathological parameters, including histological type, pathological grade, and microvessel density (MVD), determined using CD34-labelling. Expression of DLL4, VEGF and HIF-1α was very strong in gliomas, relative to normal tissues, linked with the malignant grade. Moreover, DLL4 staining positively correlated with VEGF and HIF-1α expression and with MVD. Thus our results indicate that DLL4 represents a potential biomarker and therapeutic target for glioma angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Calcium-Binding Proteins
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / blood supply
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunohistochemistry / methods
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Male
  • Microvessels / metabolism
  • Microvessels / pathology
  • Middle Aged
  • Neoplasm Staging / methods
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • DLL4 protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Intercellular Signaling Peptides and Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A