Role of VEGF-Flt-1 signaling in malignant behaviors of oral cancer

Vascular endothelial growth factor (VEGF) plays a critical role in tumor angiogenesis. VEGF and its receptor FLT-1 signaling may contribute to cell migration of macrophages, osteoclasts and some tumor cells. However, the direct role of VEGF-Flt-1 signaling in malignant behaviors of oral squamous cell carcinoma (OSCC) is not well understood. To clarify the effects of VEGF-Flt-1 signaling in OSCC bone invasion, VEGF expression in OSCC cells and number of Flt-1+ osteoclasts at bone invasion front in 55 gingival OSCC cases were evaluated by immunohistochemistry. Twenty-four of 55 cases (43.63%) strongly expressed VEGF. The VEGF highly expressing cases were statistically correlated with the increased number of Flt-1+ osteoclasts and the more aggressive radiographic pattern of bone invasion ( p In conclusion, VEGF-Flt-1 signaling promotes osteoclastogenesis, proliferation and facilitating invasion and migration of OSCC through production of MMP-1 and 3. Blocking of VEGF-Flt-1 signaling may be beneficial for OSCC treatment.