Tumor cell-derived placental growth factor sensitizes antiangiogenic and antitumor effects of anti-VEGF drugs

摘要: The role of placental growth factor (PlGF) in modulation tumor angiogenesis and remains an enigma. Furthermore, anti-PlGF therapy controversial preclinical models. Here we show that both human mouse tumors, PlGF induced the formation dilated normalized vascular networks were hypersensitive to anti-VEGF anti–VEGFR-2 therapy, leading dormancy a substantial number avascular tumors. Loss-of-function using plgf shRNA choriocarcinoma significantly accelerated rates acquired resistance drugs, whereas gain-of-function increased sensitivity. Further, VEGFR-2 VEGFR-1 blocking antibodies displayed opposing effects on angiogenesis. blockade genetic deletion tyrosine kinase domain resulted enhanced These findings demonstrate tumor-derived negatively modulates may potentially serve as predictive marker cancer therapy.