The CD46 Knockout A2780 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population engineered to disrupt the CD46 gene in the A2780 human ovarian carcinoma cell line. This loss-of-function model enables investigation of CD46-mediated complement regulation, immune modulation, and pathogen interaction without the constraints of clonal selection. The polyclonal format preserves heterogeneous knockout events across the population, providing a robust tool for studies where diverse editing outcomes are advantageous. As a pool of edited cells, this product facilitates functional genomics, drug target validation, and mechanistic dissection of CD46-dependent pathways in a therapeutically relevant cancer model.
The A2780 cell line, established from an untreated patient with ovarian carcinoma, is a widely acknowledged model in ovarian cancer research. These adherent epithelial cells exhibit characteristic oncogenic signaling and are extensively employed to study tumor biology, drug resistance, and metastatic mechanisms. Their human origin and well-documented responsiveness to chemotherapeutic agents render them particularly suitable for translational investigations. In the context of CD46 knockout, A2780 cells provide a clinically pertinent backdrop to examine how complement regulatory proteins influence ovarian tumor progression and immune evasion strategies.
CD46, also known as membrane cofactor protein (MCP), is a type I transmembrane glycoprotein that safeguards host cells from autologous complement attack. It functions as a cofactor for the serine protease Factor I to cleave the complement components C3b and C4b, thereby preventing formation of the membrane attack complex. Beyond complement inhibition, CD46 serves as a receptor for several pathogens, including measles virus hemagglutinin, human herpesvirus 6 glycoproteins, and adenovirus fiber protein, and participates in T-cell regulation. Signaling downstream of CD46 involves activation of Src family kinases and the small GTPase Rac, modulating cytokine production such as IL-10 and influencing CD4+ T-cell differentiation. Expression of CD46 is upregulated by inflammatory stimuli including TNF-??, IFN-??, and IL-10, linking it to the tumor microenvironment.
In ovarian carcinoma, CD46 is often overexpressed, contributing to immune evasion by protecting tumor cells from complement-dependent cytotoxicity and potentially dampening anti-tumor T-cell responses. The A2780 knockout model enables dissection of these protective mechanisms, providing a platform to assess how loss of CD46 sensitizes ovarian cancer cells to complement-mediated lysis or alters tumor-immune interactions. This model is particularly relevant for exploring therapeutic strategies that target CD46, such as antibody?Cdrug conjugates or oncolytic viruses that exploit CD46 as an entry portal. By eliminating CD46 function, researchers can delineate its specific contributions to ovarian cancer cell survival, proliferation, and drug sensitivity.
The CD46 knockout A2780 polyclonal cells are amenable to a wide array of downstream assays. Flow cytometry can confirm loss of surface CD46 expression and assess changes in complement deposition. Complement-dependent cytotoxicity assays gauge the functional consequence of CD46 disruption. Viral infection assays using measles or adenoviral vectors clarify CD46-dependent entry mechanisms. Additional applications include Western blot for signaling analysis, RT-qPCR for gene expression profiling, cell proliferation and invasion assays to evaluate phenotypic changes, and drug sensitivity testing to identify synergistic vulnerabilities. For further information on this validated knockout model, please contact Ascent Research.
