The ITGAM Knockout AGS Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal cell population derived from the AGS human gastric adenocarcinoma epithelial cell line, designed for loss-of-function studies of integrin alpha M (CD11b). Following CRISPR/Cas9-mediated disruption of the ITGAM gene, the resulting knockout model lacks CD11b protein expression, thereby abolishing the formation of the Mac-1 (complement receptor 3) heterodimer with CD18 and enabling investigation of ITGAM-dependent functions in a gastric epithelial context.
The AGS parental cell line originates from a gastric adenocarcinoma biopsy of a 54-year-old female donor and is widely employed as a model system for gastric epithelial biology and gastric cancer research. These adherent epithelial cells endogenously express molecules involved in integrin-mediated adhesion and signaling, making them suitable for analyzing the impact of ITGAM deletion on pathways governing cell?Cmatrix interactions, migration, and immune-related processes within the stomach epithelium.
ITGAM encodes integrin alpha M (CD11b), which dimerizes with integrin beta 2 (CD18) to form the Mac-1 receptor. Mac-1 functions as a complement receptor (CR3) binding iC3b and also recognizes ICAM-1, fibrinogen, and other ligands, thereby mediating cell adhesion, migration, and phagocytosis. In response to upstream regulators such as TNF-??, IL-1??, TGF-??, and transcriptional activators PU.1 and C/EBP, CD11b expression is modulated. Upon ligand engagement, Mac-1 activates downstream signaling cascades involving FAK, Src, Syk, PI3K, AKT, NF-??B, and MAPK, as well as Rho GTPase-driven cytoskeletal rearrangements. Intracellular adaptors talin and kindlin are critical for integrin inside-out activation. By eliminating CD11b, this knockout model disrupts the entire Mac-1 signaling axis and associated effector functions.
In the AGS gastric cancer cell line, heterologous expression of CD11b or CD11b-like integrins has been reported in certain contexts, potentially contributing to tumor cell adhesion to extracellular matrix coatings containing iC3b or fibrinogen, and influencing invasive capacity. Loss of ITGAM in AGS polyclonal cells provides a relevant platform to interrogate the tumor-intrinsic roles of CD11b in gastric adenocarcinoma, including its involvement in pro-survival signals, migration on ICAM-1-presenting surfaces, and modulation of immune cell recruitment via complement fragment interactions. As a polyclonal knockout population, this reagent mitigates selection pressures and clonal artifacts, offering a more representative loss-of-function model for integrative studies combining biochemistry, imaging, and functional assays within the gastric cancer milieu.
Researchers can employ ITGAM Knockout AGS Polyclonal Cells to dissect CD11b-dependent adhesion on immobilized ICAM-1 or iC3b, quantify changes in migratory and invasive capacity through transwell or wound-healing assays, and analyze integrin-proximal signaling events by assessing phosphorylation of FAK (Tyr397), AKT, and Src family kinases. Complement binding and phagocytic uptake of opsonized particles may be monitored to evaluate residual CR3 function. This polyclonal knockout model is also suitable for co-culture experiments with immune cells to study gastric epithelial-immune crosstalk during inflammation or tumorigenesis, and for drug screening targeting integrin-mediated pathways. For further details, please contact Ascent Research.
