APLN and neoplasm: Our studies demonstrated that VEGFA and APLN are co-expressed in GBM hypoxic areas [14,15], that blockade of VEGFA/VEGFR2 signaling (using bevacizumab or ramucirumab) downregulates APLN [65], and that blockade of VEGFA/VEGFR2 and attenuation of APLN-levels synergistically reduce tumor angiogenesis but also increased tumor cell invasion [42,66].