The ARG1 Knockout A2780 Polyclonal Cells are a heterogeneous population of CRISPR/Cas9-edited A2780 human ovarian cancer cells with targeted disruption of the ARG1 gene. This polyclonal knockout model provides a biologically averaged loss-of-function system, avoiding clonal artifacts and enabling robust functional studies of arginase 1 in a relevant epithelial context.
The A2780 parental cell line was derived from an untreated patient with ovarian endometrioid adenocarcinoma and retains key epithelial characteristics, making it a widely used model for ovarian cancer biology. It responds to cytokine signals, supports tumor?Cimmune interaction studies, and is employed in investigations of signal transduction, metabolic reprogramming, and therapeutic resistance.
ARG1 encodes arginase 1, a manganese-dependent enzyme that hydrolyzes L-arginine to L-ornithine and urea, a pivotal reaction of the urea cycle. In the tumor microenvironment, ARG1 expression is upregulated by interleukin-4 (IL-4) and IL-13 via STAT6, with additional regulation by IL-10, TGF-beta, and Toll-like receptor ligands. The enzyme functions as a homotrimer and interacts with RACK1, while its activity depletes local arginine, limiting substrate for nitric oxide synthase (NOS) and suppressing T-cell receptor signaling through reduced arginine availability. Ornithine produced by ARG1 is converted by ornithine decarboxylase (ODC) into polyamines, which promote cell proliferation and immune evasion. Consequently, ARG1 operates as an immune checkpoint that integrates cytokine signaling with metabolic control of T-cell function.
ARG1 knockout in A2780 cells allows dissection of arginine metabolism??s impact on tumor cell proliferation, migration, and immune modulation. Loss of arginase 1 can restore extracellular arginine concentrations, potentially relieving T-cell suppression in co-culture models, and may perturb polyamine biosynthesis and mTOR signaling. This model also facilitates analysis of compensatory metabolic shifts and evaluation of ARG1 as a therapeutic target in ovarian cancer.
Applications include confirmation of gene disruption by western blotting and RT-qPCR, measurement of arginase enzymatic activity, and functional co?culture assays with primary T cells to assess recovery of proliferation and effector functions. The cells are also suitable for metabolic profiling of arginine/ornithine ratios, flow cytometry for immune checkpoint markers, and drug sensitivity testing for arginine deprivation therapies. This polyclonal knockout population supports functional genomics screens and investigation of combinatorial strategies targeting both ARG1 and immune checkpoints. For technical inquiries, contact Ascent Research.
