RT Journal Article SR Electronic T1 A Potential Role for Vascular Endothelial Growth Factor-D as an Autocrine Growth Factor for Human Breast Carcinoma Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 701 OP 707 VO 25 IS 2A A1 AKAHANE, MANABU A1 AKAHANE, TAKEMI A1 SHAH, AMY A1 OKAJIMA, EIJIRO A1 THORGEIRSSON, UNNUR P. YR 2005 UL http://ar.iiarjournals.org/content/25/2A/701.abstract AB 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. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved