, MSD, S A , Janssen, S A , Abbott, S A ; Grant/Research Support:

, MSD, S.A., Janssen, S.A., Abbott, S.A.; Grant/Research Support: Ferrer, S.A. The following people have nothing to disclose:

Marta García-Valdecasas, Antonio Gil-Gómez, Angela Rojas, Jordi Muntané, Farncisco Javier PAdillo Ruiz, Jose Antonio Del Campo Background: Metabolic syndrome (MS) is a major risk factor for hepatocellular carcinoma (HCC), but the specific molecular pathways of tumorigenesis are incompletely understood in this context. Plasmatic Fatty Acid-Binding Protein 4 (FABP4) levels, a mediator of lipid trafficking in adipocytes, are increased in patients with MS and correlated PARP inhibitor with lesions of non alcoholic steatohepatitis, suggesting a potential role for FABP4 in liver pathogenesis related to MS. In addition, some experimental studies have shown that FABP4 may have an oncogenic potential. The aim of our study was to investigate FABP4 expression and its role in liver carcinogenesis related to MS. Material & Methods FABP4 expression was investigated by Western Blot, immunohistochemistry and RT-PCR on human Lenvatinib HCC and non-tu-moral liver samples related to MS, and compared with samples from patients having

Hepatitis C Virus (HCV) chronic liver disease. Role and regulation of FABP4 were in vitro assessed on cell cultures using HepG2 and HUVEC cells. Results: By contrast to mRNA level, FABP4 protein expression was significantly upregulated in human HCCs related to MS compared to HCCs associated

with HCV infection (4-fold, p=0.01). FABP4 expression was inversely correlated with the number of tumoral nodules and vascular invasion in HCCs related to MS. In patients with MS, FABP4 expression was increased in HCC samples compared with non-tumoral samples (p<0.01). Using double immunostaining, FABP4 expression was restricted to endo-thelial cells in HCC samples. Consequently, we investigated FABP4 regulation in endothelial cells using HUVEC. In HUVEC cells, FABP4 expression was significantly increased by VEGF (25 and 50 ng/ml for 24h, 6- and 14-fold increase, respectively, p<0.01) and Glucose (25 mM for 4 and Selleckchem Erastin 24h, 3-fold increase, p<0.01). Protumoral effects of FABP4 were evaluated in HepG2 cells. In presence of recombinant FABP4 (100 and 200 ng/ml), decreased caspase 3 expression, increased cell proliferation and migration were observed in HepG2 cells (p<0.01). Conclusion: Our results highlight the contribution of endothelial cells in the aggressiveness of HCC via FABP4 upregulation and suggest the potential of FABP4 targeting in patients with MS. Disclosures: The following people have nothing to disclose: Aurelie Sannier, Samira Laouirem, Mouna Mebarki, Miguel Albuquerque, Jacques Belghiti, Pierre Bedossa, Valerie Paradis NAFLD is associated with increased risk of development of end stage liver disease and cirrhosis, and can be complicated by hepatocellular carcinoma (HCC).

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