Abstract
Abstract 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 and over expression 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 significantly reduced invasion, migration and wound healing behaviors of HCC cell lines. Overexpression of CCDC80 was increased invasion and migration. 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. The mouse xenograft model also has shown the lower tumor growth, tumor weight and metastatic tumor nodule number in CCDC80 knockdown HSC with HCC co-injection compared with normal HSC and HCC co-injected mouse. 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-Suck Kim, SaeHwan Lee, Nayoung Jun, Hyog Young Kwon. Secreted CCDC80 from hepatic stellate cells promote metastasis of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5165.
Published Version
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