Abstract 3862: The potential role of CD44 in liver regeneration

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background and Aim: Liver regeneration occurs after liver damage by ischaemia, hepatitis, or in hepatocellular carcinoma (HCC) patients receiving hepatic resection or liver transplantation. Understanding the molecular bases of this process will provide novel therapeutic approaches for patients with various liver diseases. Previous studies suggested the linkage between CD44, a multifunctional cell surface receptor, and liver regeneration. The detailed role of this receptor in liver regeneration, however, remained unclear. The present study aimed at elucidating the role of CD44 in liver regeneration. Materials and Methods: A mouse model of liver regeneration induced by partial hepatectomy (PH) was employed. Serum and liver tissues were collected at different time points after PH. ELISA was performed to measure hyaluronic acid (ligand for CD44) level in serum. Flow cytometry was done to characterize liver cell populations after PH. Liver regeneration was quantified by measurement of liver mass and by immunohistochemical staining for PCNA (a proliferation marker). Quantitative PCR was performed to compare gene expression pattern of 46 genes between CD45− CD44+ cells and their CD44− counterparts. Results: Firstly, serum hyaluronic acid level was elevated at the early stage of liver regeneration. Secondly, by flow cytometry, an increase in CD45− CD44+ cell population was found. Thirdly, immunohistochemical analysis revealed active hepatocyte proliferation during this period. Interestingly, the hepatectomy-induced cell proliferation was suppressed after treating mice with anti-CD44 antibody, suggesting a functional role of CD44 in liver regeneration. Lastly, dysregulation of genes involving in cell proliferation, angiogenesis, and metabolism of hyaluronic acid was disclosed in CD45− CD44+ cells. Conclusion: The present study indicated that CD44-mediated pathways are required for liver regeneration, which may have therapeutic implications in treating liver diseases, including HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3862. doi:1538-7445.AM2012-3862