The ICAM1 Knockout DLD-1 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human DLD-1 colorectal adenocarcinoma cell line, featuring targeted disruption of the intercellular adhesion molecule 1 (ICAM1) gene. This product provides a heterogeneous pool of edited cells, offering a robust loss-of-function model for investigating ICAM1-mediated processes in an epithelial cancer context.
The parental DLD-1 cell line originates from a human colorectal adenocarcinoma with Dukes?? type C classification and stable microsatellite status, representing an established model for colorectal cancer epithelial research. These adherent cells retain key characteristics of colorectal tumor epithelium, including expression of epithelial markers and the ability to form intercellular junctions, making them suitable for studying cell adhesion dynamics, tumor microenvironment interactions, and signaling pathways relevant to cancer progression.
ICAM1 functions as a transmembrane glycoprotein that mediates heterotypic cell adhesion by binding to integrins LFA-1 (??L??2) and Mac-1 (??M??2) on leukocytes, facilitating their firm adhesion and diapedesis across endothelia. In response to pro-inflammatory stimuli such as TNF??, IL-1??, and IFN??, ICAM1 expression is upregulated via NF-??B and AP-1 transcription factors. Upon engagement, ICAM1 triggers intracellular signaling cascades involving activation of Src family kinases and Rho GTPases, promoting cytoskeletal reorganization, and stimulates MAPK pathways including p38 and ERK1/2, which contribute to inflammatory gene expression and cell motility. Additionally, ICAM1 participates in immune synapse formation and co-stimulatory signaling in T cells, and serves as a receptor for human rhinovirus and Plasmodium falciparum-infected erythrocytes.
In the DLD-1 colorectal adenocarcinoma model, targeted disruption of ICAM1 abrogates the cell surface receptor critical for leukocyte adhesion and transmigration, thereby perturbing inflammatory cell recruitment cues that are often hijacked by tumor cells. Loss of ICAM1 is anticipated to attenuate homotypic and heterotypic cell adhesion, impairing cross-talk with immune cells and extracellular matrix components within the tumor microenvironment. Given the established role of ICAM1 in promoting metastatic dissemination through enhanced adhesion to leukocytes and endothelial cells, this knockout model provides a valuable tool to dissect the contribution of ICAM1 to colorectal cancer cell migration, invasion, and interaction with host immune cells.
This ICAM1 knockout pool is ideally suited for functional studies employing flow cytometry to confirm loss of ICAM1 surface expression, leukocyte adhesion and transmigration assays using fluorescently labeled immune effector cells, and immunofluorescence microscopy to examine junctional protein redistribution. Researchers can utilize Western blotting and RT-qPCR to validate downstream signaling perturbations, such as reduced ERK1/2 or p38 phosphorylation upon cytokine stimulation, and assess inflammatory marker expression. The model enables exploration of ICAM1-dependent pathways in inflammatory bowel disease, rheumatoid arthritis, and atherosclerosis contexts, as well as investigation of rhinovirus or malaria parasite entry mechanisms. Furthermore, the DLD-1 background facilitates screening of anti-metastatic or anti-inflammatory compounds by quantifying changes in adhesion, migration, and signaling in a colorectal cancer epithelial context. For additional information, please contact Ascent Research.
