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

Arianna Aricò,Fulvio Riondato,Maria Elena Gelain,Barbara C Rütgen,Stefano Comazzi,Mauro Dacasto,Sabine E Essler,Massimo Castagnaro,Mery Giantin,Luca Aresu

doi:10.1186/1746-6148-9-94

Abstract

BackgroundCanine 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.ResultsMT1-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.ConclusionsThis 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.

Highlights

Canine lymphoma represents the most frequent haematopoietic cancer and it shares some similarities with human non-Hodgkin lymphoma
In a previous work in dogs, we demonstrated that plasma levels of Matrix metalloproteinases (MMP)-9 and vascular endothelial growth factor (VEGF) are higher in B-cell and T-cell lymphomas with respect to healthy dogs and that their levels significantly decreased in B-cell lymphomas during chemotherapy [13]
Higher MMP-9 and Tissue inhibitors of matrix metalloproteinase (TIMP)-1 mRNA expression levels were observed in T-cell lymphomas compared to B-cell lymphomas and healthy controls (p

Summary

Introduction

Canine lymphoma represents the most frequent haematopoietic cancer and it shares some similarities with human non-Hodgkin lymphoma. Different reports in human medicine have shown that lymphoproliferative tumours are able to produce extra cellular matrix (ECM)-degrading enzymes with proteolytic activity. In this context, matrix metalloproteinases (MMPs) have been demonstrated to have a role in the pathogenesis of lymphoma and be of prognostic significance [3,4]. MMPs are zinc-dependent enzymes responsible for the degradation of the ECM components, functional component of the angiogenic switch during carcinogenesis, increasing the availability of vascular endothelial growth factor (VEGF) in a sort of vicious circle [9]. VEGF has two potential roles: increase of angiogenesis and proliferation and/or survival of lymphoma cell induced by autocrine vascular endothelial growth factor receptor-mediated signalling [9]

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