Journal of Hepatology vol:58 issue:2 pages:319-328
The placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF)-family known to stimulate endothelial cell growth, migration and survival, attract angiocompetent macrophages and determine the metastatic niche. Unlike VEGF, genetic studies have shown that PlGF is specifically involved in the pathologic angiogenesis, thus its inhibition would not affect healthy blood vessels, providing an attractive drug candidate with a good safety profile. In this study, we assess whether inhibition of PlGF could be used as a potential therapy against hepatocellular carcinoma (HCC), by using PlGF-knock out mice and monoclonal anti-PlGF antibodies in a mouse model for HCC. In addition, the effect of PlGF-antibodies is compared to that of sorafenib, as well as the combination of both therapies. In our study we have found that both in a transgenic knock out model as in a treatment model, targeting PlGF significantly decreased tumour burden. This was achieved not only by inhibiting neo-vascularisation, but also by decreasing hepatic macrophage recruitment and by normalizing the remaining blood vessels, thereby decreasing hypoxia and reducing the pro-metastatic potential of HCC. CONCLUSION: Considering the favourable safety profile and its pleiotropic effect on vascularisation, metastasis and inflammation, PlGF-inhibition could become a valuable therapeutic strategy against HCC.