The ARG1 Knockout Ca Ski Polyclonal Cells product consists of a polyclonal population of Ca Ski cervical carcinoma cells with CRISPR/Cas9-mediated disruption of the ARG1 locus. This engineered pool abrogates arginase 1 function, blocking the conversion of L-arginine to urea and ornithine, and establishes a loss-of-function model suitable for dissecting metabolic and immunoregulatory roles in cancer. Generated as a heterogeneous knockout population rather than a monoclonal isolate, the cells capture the diversity of editing events and are delivered as a stable, ready-to-use reagent for downstream applications.
The Ca Ski host cell line is an adherent epithelial line derived from a cervical squamous cell carcinoma metastasis and contains integrated HPV-16 genomes. The sustained expression of E6 and E7 viral oncoproteins inactivates p53 and pRB tumor suppressors, respectively, promoting unchecked cell cycle progression and genomic instability. This well-characterized line serves as a classic model for HPV-related carcinogenesis, recapitulating key features of cervical cancer pathogenesis, including altered apoptotic pathways and immune evasion strategies that are central to tumor progression.
Arginase 1 (ARG1) hydrolyzes L-arginine to urea and ornithine, functioning in the urea cycle. It is regulated by cytokines IL-4, IL-10, IL-13, TGF-?? via transcription factors STAT6, C/EBP-??, PPAR-??, and toll-like receptor ligands. By depleting arginine, ARG1 competes with NOS2, suppressing nitric oxide synthesis and promoting T-cell anergy. Its product ornithine drives polyamine (via ODC1) and proline synthesis. ARG1 interacts with manganese cofactor and agmatinase, with pathway partners including OTC, mTORC1, and SLC7A5, linking metabolism to immune checkpoint control.
In the HPV-16-positive Ca Ski model, ARG1 knockout eliminates arginase activity, elevating arginine and favoring NOS2-mediated nitric oxide synthesis, which can activate immune mechanisms and relieve T-cell suppression. Reduced ornithine shuts down polyamine and proline production, impairing proliferation and stromal remodeling. This mirrors therapeutic arginase inhibition and reveals metabolic-immune crosstalk in cervical cancer.
Applications include T-cell co-culture for immunosuppression studies, LC-MS metabolomics for arginine/ornithine, Griess assay for nitric oxide, RT-qPCR and western blot for knockout validation, viability assays under arginine limitation, and flow cytometry for immune checkpoint markers. It supports arginine deprivation therapy target validation and HPV cancer models. For further details, contact Ascent Research.
