LAUSR

Liver cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC) and hepatic stellate cell (HSC) has pivotal role in developing cirrhosis by producing various extracellular matrix (ECM). HSC are essential mediators of tumor microenvironment of HCC through remodeling of ECM and angiogenesis. We found that CCDC80 expression is upregulated in activated HSCs from RNA-sequencing with human fetal stellate cell. However, the role of CCDC80 was not well known in hepatocarcinogenesis. First, we validated mRNA expression of CCDC80 was increased in activated HSC lines and protein expression was also increased in cultured media. Functional analysis of knockdown CCDC80 was investigated in both HCC and HSC cell lines, and HCC cell lines were analyzed for proliferation (MTT assay), migration (using transwell), invasion (using Matrigel-coated transwell), and wound healing assay with condition media of CCDC80 knockdown HSCs. Expression of epithelial-mesenchymal transition (EMT) markers in HCC was evaluated with conditioned media. Knockdown of CCDC80 resulted in reduced cell proliferation and significantly reduced invasion, migration and wound healing behaviors of HCC cell lines. Expression of E-cadherin was increased and snail and vimentin expression were decreased in HCC cell lines cultured with conditioned media of CCDC80 knockdown HSCs. The associations between CCDC80 and EMT markers were validated in CCDC80 transfected HSC cell line compared with control. Taken together, secreted CCDC80 from HSCs affected the aggressiveness and EMT of HCC cell lines. CCDC80 might be a novel biomarker and therapeutic target for patients with HCC. Citation Format: Kwang Seock Kim, SaeHwan Lee, Nayoung Jun, Hyog Young Kwon. Secreted ccdc80 from hepatic stellate cell promote invasion and epithelial-mesenchymal transition in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5148.