Matrix methalloproteinases and vascular endothelial growth factor in canine lymphohematopoietic malignancies

Introduction Canine lymphohematopoietic malignancies are common spontaneous diseases whose biologic behavior closely resemble their human counterparts. 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 hematological malignancies. Aim of this study was to investigate mRNA and protein expression of most relevant MMPs and VEGF in canine lymphohematopoietic malignancies. Methods Lymph node aspirates from 26 B-cell and 21 T-cell lymphoma and peripheral blood samples from 11 cases of acute lymphoblastic leukemia (ALL) and 12 of chronic lymphocytic leukemia (CLL) were collected. MMP-9, MMP-2 and VEGF-A protein expressions were evaluated by immunocytochemistry, while MMP-2, MMP-9, MT1-MMP, TIMP-1, TIMP-2, RECK, VEGF-A and VEGF-164 mRNA levels using quantitative RT-PCR. Results Higher MMP-9 and VEGF-A values were noticed at mRNA and protein level in leukemia versus lymphoma dogs and in T-cell versus B-cell lymphoma. Furthermore, MT1-MMP, TIMP-1 and RECK mRNA amounts were significantly higher in T-cell lymphoma respect to B-cell counterpart. In the leukemic group, TIMP-2 mRNA was significantly over-expressed in ALL. Positive and significant correlations were found between MMP-9 and TIMP-1, and MMP-9 and VEGF-A in CLL and in T-cell lymphoma, then among MMP-2, MT1-MMP and TIMP-2 in T-cell lymphoma. Conclusions The present study suggests a potential role of MMP-9, MT1-MMP, TIMP-1, TIMP-2 and VEGF in tissue migration, angiogenesis and anti-apoptotic activity. Our results show that expression of these markers is associated with type of leukemia (acute vs chronic) and immunophenotype of lymphoma (B vs T).