Abstract 3982: Anti-Stanniocalcin 1 antibody as a potential therapeutic strategy for liver fibrosis and hepatocellular carcinoma

Abstract

Abstract Introduction: Hepatocellular carcinoma (HCC) is the sixth most frequently diagnosed cancer and the third leading cause of cancer deaths. Liver fibrosis (LF) is a progressive disease and cirrhosis, the advanced stage of LF, is per se a risk factor for HCC. Moreover, LF persists after the development of HCC. Stanniocalcin 1 (STC1), as a serum biomarker of both HCC and LF as we previously reported, was found to be secreted from HCC cells and hepatic stellate cells (HSCs). STC1 promoted cell migration and invasion of HCC and activation of HSCs, suggesting that STC1 could be an actionable target of both diseases. As a secretory protein, STC1 could potentially be targeted by an antibody approach. Objectives: This study aims to investigate the therapeutic values of targeting secretory STC1 in HCC and LF models using antibody approach, including in the interplay between HSCs and HCC cells. Methods: Human anti-STC1 antibody was harvested and purified from a hybridoma cell line of a designed epitope. In vitro transwell migration and invasion assays were performed on human HCC cell lines. Co-culture assays were set up with HCC cells cultured in conditioned medium (CM) collected from LX2, a human HSC cell line. Expression of fibrogenic markers were measured by western blotting, qPCR and ELISA. Results: Enforcement of STC1, either by viral transfection of STC1-overexpressing vector or by the treatment of recombinant STC1 protein, increased the migration and invasion of HCC cells. The effects were abrogated by the co-treatment of anti-STC1 antibody. The enhanced migratory and invasive abilities of HCC cells induced by activated HSC CM were abolished by anti-STC1 antibody. In addition, anti-STC1 antibody suppressed the secretion of type I collagen (COL1) and the intracellular expression of fibrogenic markers alpha-smooth muscle actin (ɑSMA) and TIMP metallopeptidase inhibitor 1 (TIMP1) in TGFβ1-activated HSCs. Conclusion: Anti-STC1 antibody displays therapeutic effects on HCC in vitro. It is also shown to suppress the expression of fibrogenic markers in activated HSCs. Anti-STC1 antibody is a potential therapeutic strategy for both HCC and LF. Citation Format: Alfred Long-Hin Suen, Kristy Kwan-Shuen Chan, Regina Cheuk-Lam Lo. Anti-Stanniocalcin 1 antibody as a potential therapeutic strategy for liver fibrosis and hepatocellular carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3982.