Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10751774 | Biochemical and Biophysical Research Communications | 2015 | 7 Pages |
Abstract
The hepatocyte growth factor and its receptor c-Met are correlated with castration-resistance in prostate cancer. Although HGF has been considered as an attractive target for therapeutic antibodies, the lack of cross-reactivity of monoclonal antibodies with human/mouse HGFs is a major obstacle in preclinical developments. We generated a panel of anti-HGF RabMAbs either blocking HGF/c-Met interaction or inhibiting c-Met phosphorylation. We selected one RabMAb with mouse cross-reactivity and demonstrated that it blocked HGF-stimulated downstream activation in PC-3 and DU145 cells. Anti-HGF RabMAb inhibited not only the growth of PC-3 cells but also HGF-dependent proliferation in HUVECs. We further demonstrated the efficacy and potency of the anti-HGF RabMAb in tumor xenograft mice models. Through these in vitro and in vivo experiments, we explored a novel therapeutic antibody for advanced prostate cancer.
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Authors
Yanlan Yu, Yicheng Chen, Guoqing Ding, Mingchao Wang, Haiyang Wu, Liwei Xu, Xuefang Rui, Zhigen Zhang,