Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Gastroenterology & Hepatology, angiogenesis, biliary tumours, placental growth factor, prolyl hydroxylase containing domain, vascular endothelial growth factor, INTRAHEPATIC CHOLANGIOCARCINOMA, ANGIOGENESIS, EXPRESSION, LIVER, SORAFENIB, RECEPTOR, CANCER, CELLS, Animals, Antibodies, Monoclonal, Bile Duct Neoplasms, Carcinoma, Hepatocellular, Cholangiocarcinoma, Hypoxia-Inducible Factor-Proline Dioxygenases, Liver Neoplasms, Experimental, Male, Mice, Mice, Knockout, Placenta Growth Factor, Pregnancy Proteins, Procollagen-Proline Dioxygenase, Treatment Outcome, Tumor Burden, 1103 Clinical Sciences, 3202 Clinical sciences

Abstract:

OBJECTIVES: Hepatocellular carcinoma and cholangiocarcinoma form the majority of primary hepatic tumours and are the third most common cause of cancer-related deaths. These liver tumours rapidly outgrow their vascular supply and become hypoxic, resulting in the production of hypoxia inducible factors and triggering the angiogenic switch. Therefore, inhibiting angiogenesis has proven to be a valuable therapeutic strategy in hepatocellular carcinoma, yet less is known about its use in cholangiocarcinoma. In this study, we assess whether inhibiting the placental growth factor (PlGF) could offer a therapeutic option in mice with hepatocellular carcinoma and cholangiocarcinoma. PlGF is a homologue of the vascular endothelial growth factor, which is only involved in pathological angiogenesis, therefore, its inhibition does not induce adverse effects. METHODS: We have used a chemically induced transgenic mouse model in which both hepatocellular carcinoma and cholangiocarcinoma develop after 25 weeks and are treated with murine monoclonal antibodies targeting PlGF. RESULTS: This study has shown for the first time that inhibiting PlGF decreases the burden of cholangiocarcinoma, by affecting both angiogenesis and inflammation. CONCLUSION: The use of monoclonal antibodies targeting PlGF could thus offer a potential systemic treatment for patients who suffer from primary liver tumours.