The CCS Knockout A2780 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the CCS gene undergoes targeted disruption, creating a robust loss-of-function model for investigating copper chaperone-mediated oxidative stress protection. This polyclonal cell product is generated through CRISPR/Cas9-mediated gene disruption in the human A2780 ovarian carcinoma cell line, resulting in a heterogeneous pool of cells with impaired CCS expression. The polyclonal nature preserves population-level heterogeneity while enabling functional studies of CCS-dependent pathways without the clonal selection artifacts associated with single-cell-derived lines.
The A2780 host cell line is a well-characterized ovarian endometrioid adenocarcinoma epithelial model derived from an untreated patient. It exhibits epithelial morphology and retains sensitivity to cisplatin, making it a widely employed system for ovarian cancer research and drug response studies. The cisplatin-sensitive background provides a defined baseline for evaluating how CCS disruption influences cellular responses to chemotherapeutic stress. These adherent cells maintain key features of ovarian carcinoma, including relevant signaling networks and redox regulatory mechanisms, ensuring physiologically meaningful experimental readouts.
CCS encodes the copper chaperone for superoxide dismutase 1 (SOD1), a critical metalloenzyme that requires copper ions for its dismutase activity. CCS specifically delivers copper to SOD1, forming a transient CCS-SOD1 heterodimer that facilitates metal transfer and enzymatic activation. Once activated, SOD1 converts highly reactive superoxide radicals into hydrogen peroxide and oxygen, protecting cells from oxidative damage and maintaining redox homeostasis. This process is regulated by upstream factors including copper ion availability, oxidative stress, and the metal-responsive transcription factor MTF1. Downstream, SOD1 activation leads to superoxide dismutation and reduced oxidative damage, with CCS, SOD1, copper, and reactive oxygen species (ROS) representing core pathway components.
Disruption of CCS in A2780 cells abrogates copper delivery to SOD1, leading to SOD1 inactivity and compromised antioxidant defense. In the context of ovarian cancer, where redox balance influences proliferation, apoptosis, and drug sensitivity, this knockout model exposes vulnerabilities in the oxidative stress response. The cisplatin-sensitive A2780 background further accentuates the impact of CCS loss, enabling researchers to dissect how copper chaperone function modulates chemoresistance mechanisms. This system also provides a platform to study the interplay between copper homeostasis and oncogenic signaling, as well as the potential for synthetic lethality strategies targeting redox pathways.
This polyclonal knockout cell product is suitable for a broad range of investigations into oxidative stress response, cancer cell redox biology, drug resistance mechanisms, and neurodegeneration modeling, particularly related to amyotrophic lateral sclerosis (ALS)-linked SOD1 dysfunction. Representative assays include Western blotting for CCS and SOD1, SOD enzymatic activity measurements, ROS detection probes, copper sensitivity assays, immunofluorescence localization of endogenous or tagged proteins, and cell viability assessments under oxidative or chemotherapeutic stress. For detailed product information, protocols, or technical support, please contact Ascent Research.
