The role of vascular endothelial growth factor and matrix metalloproteinases in canine lymphoma: in vivo and in vitro study

BMC Vet Res. 2013 May 3:9:94. doi: 10.1186/1746-6148-9-94.

Abstract

Background: Canine lymphoma represents the most frequent haematopoietic cancer and it shares some similarities with human non-Hodgkin lymphoma. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play a coordinated role during invasion and proliferation of malignant cells; however, little is known about their role in canine haematologic malignancies. The aim of this study was to investigate the mRNA and protein expression of VEGF and the most relevant MMPs in canine lymphoma. Lymph node aspirates from 26 B-cell and 21 T-cell lymphomas were collected. The protein expression levels of MMP-9, MMP-2 and VEGF-A were evaluated by immunocytochemistry, and the mRNA levels of MMP-2, MMP-9, MT1-MMP, TIMP-1, TIMP-2, RECK, VEGF-A and VEGF-164 were measured using quantitative RT-PCR.

Results: MT1-MMP, TIMP-1 and RECK mRNA levels were significantly higher in T-cell lymphomas than in B-cell lymphomas. Higher mRNA and protein levels of MMP-9 and VEGF-A were observed in T-cell lymphomas than in B-cell lymphomas and healthy control lymph nodes. A positive correlation was found between MMP-9 and VEGF-A in T-cell lymphomas. Moreover, MMP-9, MT1-MMP, TIMP-1 and VEGF-A were expressed at the highest levels in high-grade T-cell lymphomas.

Conclusions: This study provides new information on the expression of different MMPs and VEGF in canine lymphoma, suggesting a possible correlation between different MMPs and VEGF, immunophenotype and prognosis.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Dog Diseases / metabolism
  • Dog Diseases / physiopathology*
  • Dogs
  • GPI-Linked Proteins / metabolism
  • GPI-Linked Proteins / physiology
  • Lymph Nodes / metabolism
  • Lymph Nodes / physiopathology
  • Lymphoma / metabolism
  • Lymphoma / physiopathology
  • Lymphoma / veterinary*
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / physiopathology
  • Lymphoma, B-Cell / veterinary
  • Lymphoma, T-Cell / metabolism
  • Lymphoma, T-Cell / physiopathology
  • Lymphoma, T-Cell / veterinary
  • Matrix Metalloproteinase 14 / metabolism
  • Matrix Metalloproteinase 14 / physiology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 2 / physiology
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase 9 / physiology
  • Matrix Metalloproteinases / metabolism
  • Matrix Metalloproteinases / physiology*
  • Real-Time Polymerase Chain Reaction / veterinary
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / physiology
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor A / physiology*

Substances

  • GPI-Linked Proteins
  • Tissue Inhibitor of Metalloproteinase-1
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 14