The ITGB2 Knockout NCI-H1975 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout cell population of NCI-H1975 human lung adenocarcinoma cells, engineered to disrupt ITGB2 gene expression. This loss-of-function model provides a genetically mixed pool of edited cells, avoiding clonal artifacts and better representing tumor heterogeneity. The targeted disruption in the ITGB2 locus generates a null phenotype for the integrin beta-2 subunit. The product is supplied as a live cell stock suitable for expansion, banking, and downstream functional assays.
The NCI-H1975 host cell line originates from pleural effusion of a female patient with non-small cell lung adenocarcinoma and carries EGFR L858R and T790M mutations, markers of acquired tyrosine kinase inhibitor resistance. As a standard model for EGFR-mutated lung adenocarcinoma, it retains core oncogenic signaling dependencies. This genetic context is particularly useful for studying tumor progression, drug resistance, and the crosstalk between EGFR signaling and adhesion-mediated processes.
ITGB2 encodes the integrin beta-2 subunit, which heterodimerizes with CD11 alpha chains (CD11a, CD11b, CD11c, CD11d) to form leukocyte integrins like LFA-1 and Mac-1. These receptors are activated by inside-out signals via GPCRs and chemokine receptors, where talin and kindlin binding induces high-affinity conformations. Active integrins engage ICAM-1, ICAM-2, fibrinogen, and iC3b. Downstream, FAK and Src kinases activate Rho GTPases (Rac1, Cdc42), MAPK, and NF-??B pathways. Thus, ITGB2 mediates adhesion, migration, and immune signaling, regulated by TNF-alpha and IL-8.
In NCI-H1975 cells, ITGB2 knockout disrupts integrin-mediated adhesion, potentially reducing tumor cell engagement with endothelial and matrix components. Though primarily leukocyte-associated, ITGB2 expression in certain cancers has been implicated in metastasis and immune evasion. This knockout model enables dissection of beta-2 integrin functions in cancer cell autonomous behaviors and potential crosstalk with the immune microenvironment, allowing investigation of how integrin loss influences EGFR-driven pathways and invasive properties.
This polyclonal knockout cell pool suits various applications, including adhesion and migration studies on ICAM-1 surfaces, Transwell/Matrigel invasion assays, and co-culture with immune cells to assess tumor-immune interactions. Target disruption confirmation via Western blot and flow cytometry can be coupled with immunoprecipitation, phospho-protein analysis, and RNA-seq. Drug sensitivity testing further enables target validation. For more information, contact Ascent Research.
