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Vascular endothelial growth factor and receptors in canine mastocytoma cells
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Mastocytomas are the most common malignant neoplasias in dogs and much more aggressive than in other species. Recently, the expression of vascular endothelial growth factor (VEGF) - a major regulator of angiogenesis and a potential autocrine growth factor for neoplastic cells in various malignancies - and its receptors have been investigated. These neoplasies show a very unusual expression!
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In the present study, we have investigated expression of VEGF and VEGF receptors in canine mastocytomas and the canine mastocytoma cell line C2.
As assessed by immunostaining of tissue sections and cytospin slides, primary neoplastic mast cells (MC) and C2 cells were found to express the VEGF protein.
In Northern blot and RT-PCR experiments, C2 cells expressed VEGF mRNA in a constitutive manner. VEGF mRNA expression in C2 cells was counteracted by LY294002 and rapamycin, suggesting involvement of the PI3-kinase/mTOR pathway.
Moreover, C2 cells were found to express VEGF receptor-1 (Flt-1) and VEGF receptor-2 (KDR).
However, recombinant VEGF failed to promote (3)H-thymidine uptake in C2 cells, and a neutralizing anti-VEGF antibody (bevacizumab) failed to downregulate spontaneous proliferation in these cells.
In addition, rapamycin decreased the expression of VEGF in C2 cells at the mRNA and protein level without suppressing their proliferation.
Together, canine mastocytoma cells express VEGF as well as VEGF receptors. However, despite co-expression of VEGF and its receptors, VEGF is not utilized as an autocrine growth regulator by canine mastocytoma cells.
Source: Rebuzzi L, et al (2007): Detection of vascular endothelial growth factor (VEGF) and VEGF receptors Flt-1 and KDR in canine mastocytoma cells. In: Vet Immunol Immunopathol. 2007 Feb 15;115(3-4):320-33. Epub 2006 Nov 17.
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