Comparison of vascular endothelial growth factor/vascular endothelial growth factor receptor 2 expression and its relationship to tumor cell proliferation in canine epithelial and mesenchymal tumors

The vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway plays an important role in tumor angiogenesis. VEGFR2 is expressed not only in vascular endothelial cells but also in tumor cells; however, the relationship of VEGF/VEGFR2 expression and tumor proliferation has yet to be elucidated. In addition, since several studies have reported that VEGFR2 inhibitors are more effective against epithelial tumors than mesenchymal tumors, there may be a difference in VEGF/VEGFR2 expression between epithelial and mesenchymal tumors. The purpose of this study was to elucidate differences in VEGF/VEGFR2 expression between epithelial and mesenchymal tumors and the relationship of VEGF/VEGFR2 expression and proliferation in canine tumor cells. We assessed 29 epithelial and 21 mesenchymal canine tumors for microvessel density (MVD), mRNA transcription levels of von Willebrand Factor (vWF) and endoglin, expression of VEGF, VEGFR2, and phosphorylated VEGFR2 (pVEGFR2), and proliferation index (PI) using real-time reverse transcription polymerase chain reaction and immunohistochemistry. VEGFR2 expression on vascular endothelial cells, MVD, and mRNA transcription levels of vWF and endoglin were not significantly different between the two groups. However, expression of VEGF, VEGFR2, and pVEGFR2 was higher in epithelial tumors (P<0.01). Moreover, PI correlated with pVEGFR2 expression in only epithelial tumors (P<0.01, Rs=0.543). These results suggest that the activity of VEGF/VEGFR2 signaling in tumor cells is raised in epithelial tumors, and that this signaling pathway may be related to tumor cell proliferation in epithelial tumors.