The CD46 Knockout SK-HEP-1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal cell population derived from the SK-HEP-1 human hepatocellular carcinoma cell line, engineered to disrupt the CD46 gene. This product provides a loss-of-function model in which CD46 expression is abrogated through targeted gene disruption. The polyclonal nature of the knockout pool captures a range of editing events and cellular responses, offering a robust system for studying CD46-dependent processes without the constraints of clonal selection. The cells are suited for experiments requiring a population-level knockout of CD46 in a liver cancer context.
SK-HEP-1 is a well-characterized human hepatocellular carcinoma cell line originally isolated from the ascites of a patient with liver adenocarcinoma. It displays an epithelial morphology and retains features relevant to hepatocyte biology, making it a widely used model for liver cancer research. The cell line exhibits robust growth in culture and is amenable to genetic manipulation, facilitating the creation of knockout derivatives. Its use as a host for CD46 disruption leverages the endogenous expression of complement regulatory proteins and other immune modulators, providing a physiologically relevant background for functional studies.
CD46 is a type I transmembrane glycoprotein that serves as a critical inhibitor of complement activation on host cells. It functions as a cofactor for the serine protease factor I, promoting the proteolytic inactivation of C3b and C4b deposited on cell surfaces, thereby preventing the formation of C3 and C5 convertases and subsequent complement-mediated lysis. Beyond complement regulation, CD46 acts as an entry receptor for measles virus and group B adenoviruses through interactions with viral hemagglutinin and fiber proteins, respectively. CD46 also modulates adaptive immune responses by providing costimulatory signals to T-cells, influencing IL-10 production and T-regulatory cell induction. Expression of CD46 is upregulated by pro-inflammatory cytokines such as TNF-?? and IL-1??, and by interferons, linking its regulation to inflammatory and antiviral pathways. Intracellularly, CD46 associates with cytoskeletal adaptors moesin and ezrin, facilitating signaling downstream of ligand engagement.
In the SK-HEP-1 cell line, CD46 contributes to the immune evasion capabilities inherent to many cancers. By protecting tumor cells from complement attack, CD46 helps maintain viability in the presence of the complement cascade, which can be activated within the tumor microenvironment. Knockout of CD46 in these cells abrogates this protective mechanism, rendering them susceptible to complement-dependent cytotoxicity. Additionally, loss of CD46 eliminates the primary receptor for measles virus, blocking viral entry and enabling the use of this system to dissect oncolytic virus mechanisms. This model thus illuminates how hepatocellular carcinoma cells may manipulate complement regulators to survive immune pressures and provides a platform to explore therapeutic strategies that target these vulnerabilities.
This polyclonal knockout product is ideally applied in complement-dependent cytotoxicity assays to quantify susceptibility to complement-mediated lysis, in measles virus entry and replication studies to evaluate oncolytic virotherapy approaches, and in T-cell costimulation assays to probe immune modulatory functions. Verification of CD46 disruption can be performed via flow cytometry and Western blotting. The cells also support cell viability and proliferation assays under complement stress or viral challenge. Researchers studying the tumor microenvironment, immune checkpoint mechanisms, and complement evasion in liver cancer will find this model a valuable tool. For further technical details or ordering information, please contact Ascent Research.
