Interestingly, pigment epithelium-derived factor (PEDF), an endogenous angiogenesis inhibitor, could inhibit both endothelial cell-derived and tumor cell-derived angiogenesis by down-regulating HIF-1α in breast cancer.
Lentiviruses were used to stably express PEDF in endocrine-resistant breast cancer cell lines to determine their sensitivity to tamoxifen following PEDF re-expression.
Here, we report that phosphomimetic mutants of PEDF, which possess significantly increased antiangiogenic activity, are much more efficient than wild-type (WT) PEDF in inhibiting growth and neovascularization in MDA-MB-231 (breast cancer), HCT116 (colon cancer), and U87-MG (glioblastoma) xenograft models.
These observations collectively support the hypothesis that a lack of PEDF expression is a potent factor for the enhancement of tumor growth and angiogenesis in breast cancer.