The functionalized human serine protease granzyme B/VEGF₁₂₁ targets tumor vasculature and ablates tumor growth.

ABSTRACT: The serine protease granzyme B (GrB) induces apoptosis through both caspase-dependent and -independent multiple-cascade mechanisms. VEGF₁₂₁ binds to both VEGF receptor (VEGFR)-1 and VEGFR-2 receptors. We engineered a unique GrB/VEGF₁₂₁ fusion protein and characterized its properties in vitro and in vivo. Endothelial and tumor cell lines showed varying levels of sensitivity to GrB/VEGF₁₂₁ that correlated closely to total VEGFR-2 expression. GrB/VEGF₁₂₁ localized efficiently into VEGFR-2-expressing cells, whereas the internalization into VEGFR-1-expressing cells was significantly reduced. Treatment of VEGFR-2(+) cells caused mitochondrial depolarization in 48% of cells by 48 hours. Exposure to GrB/VEGF₁₂₁ induced apoptosis in VEGFR-2(+), but not in VEGFR-1(+), cells and rapid caspase activat

SUBMITTER: Mohamedali KA 

PROVIDER: S-EPMC3921020 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature