Granzyme B-truncated VEGF fusion protein represses angiogenesis and tumor growth of OSCC

Granzyme B-truncated VEGF fusion protein represses angiogenesis and tumor growth of OSCC:

Abstract

Objective

To evaluate the anti-tumor effects of fusion protein hGrB-TV of human granzyme B (hGrB) and truncated vascular endothelial growth factor (tVEGF) on human oral squamous cell carcinoma (OSCC) in vitro and in vivo.

Methods

The fusion protein hGrB-TV was expressed and purified from E.coli bacteria by affinity chromatography. The cytotoxcity of hGrB-TV on VEGFR-2 (Flk-1)⁺ OSCC cells was analysed in vitro. The anti-tumor therapeutic study was taken on OSCC xenofrafts in vivo.

Results

The purified hGrB-TV fusion protein was selectively internalized into VEGFR-2 (Flk-1)⁺ OSCC cells and endothelial cells. It clove inactive caspase 3 into its active p20 form. The hGrB-TV showed dose-dependent cytotoxicity on VEGFR-2⁺ SCC-9 cells. The morphological changes

and cytolysis were appeared within dozens minutes. However, No cytotoxicity was observed on VEGFR-2^- cells. The hGrB alone or tVEGF alone did not have any toxicity on SCC-9 cells. In addition, hGrB-TV treatment completely destroyed the vasculature of the chick chorioallantoic membrane (CAM) in vivo and consequently led to chick embryo development arrest. Most importantly, the fusion protein hGrB-TV inhibited tumor angiogenesis and growth of human OSCC xenografts in nude mice without any apparent toxicity.

Conclusions

The fusion protein hGrB-TV specifically inhibits angiogenesis and tumor growth of OSCC; hGrB-TV is a powerful and safe therapeutic molecule for tumor therapy.

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