A Potential Role for Vascular Endothelial Growth Factor-D as an Autocrine Growth Factor for Human Breast Carcinoma Cells

Abstract

Background. Vascular endothelial growth factor-D (VEGF-D) binds and activates vascular endothelial growth factor receptor-2 (VEGFR-2), which signals for angiogenesis, and VEGFR-3, which signals for lymphangiogenesis. Besides endothelial cells, VEGFR-2 has been detected on malignant cells, including human breast carcinoma cells. Materials and Methods. It was examined if ectopic expression of human VEGF-D affected growth of breast carcinoma cell lines in vitro and in vivo. Results. VEGF-D overexpressing clonal MCF-7 and MDA-MB-231 cell lines displayed increased proliferative activities and upregulation of cyclins A, D1 and D3, compared to the vector control. Following subcutaneous inoculation of the MDA-MB-231 cells into nude mice, growth of the VEGF-D overexpressing cells was greatly accelerated. The tumor weight gain was accompanied by increased proliferative activity, cyclin A expression and microvascular density. Conclusions. These findings suggest that VEGF-D functions both as an autocrine growth factor and a stimulator of angiogenesis in breast cancer.