The ITIH2 Knockout NCI-H1975 Polyclonal Cells consist of a CRISPR/Cas9-edited population of human NCI-H1975 lung adenocarcinoma epithelial cells with disrupted ITIH2 gene function. This polyclonal pool provides a heterogeneous knockout model, avoiding clonal selection artifacts, and is ideal for studying the loss-of-function effects of the inter-alpha-trypsin inhibitor heavy chain H2.
The parental NCI-H1975 cell line is a widely used non-small cell lung cancer (NSCLC) model harboring an EGFR L858R/T790M double mutation, which drives oncogenic signaling and confers resistance to first-generation EGFR inhibitors. Its epithelial origin and aggressive phenotype make it a relevant platform for investigations into tumor progression and drug resistance mechanisms.
ITIH2 encodes the heavy chain of the inter-alpha-trypsin inhibitor (I??I) complex, which covalently binds hyaluronan to stabilize extracellular matrix structure. The I??I complex, comprising ITIH2, bikunin, and additional heavy chains (ITIH1, ITIH3, ITIH4), is formed through TSG-6-mediated transfer of heavy chains to hyaluronan. This process is stimulated by pro-inflammatory cytokines such as TNF-alpha and IL-6, acting via NF-kB and TGF-beta signaling. Downstream, the stabilized hyaluronan matrix influences CD44 clustering, activation of matrix metalloproteinases such as MMP-9, and the function of integrins and other adhesion receptors, thereby modulating cell migration and inflammatory responses.
In EGFR-mutant lung adenocarcinoma, ITIH2-mediated matrix stabilization is likely implicated in tumor invasion and metastasis. Knocking out ITIH2 in NCI-H1975 cells is expected to disrupt hyaluronan network integrity, potentially impairing migratory and invasive capacity and altering responses to inflammatory stimuli. This model enables dissection of how matrix remodeling intersects with oncogenic EGFR signaling and contributes to cytokine-driven tumor microenvironments.
These polyclonal knockout cells are suited for functional studies including Transwell migration/invasion assays, wound healing tests, and hyaluronan-binding experiments, as well as molecular analyses by western blotting, qRT-PCR, co-immunoprecipitation, and immunofluorescence. Key research applications encompass extracellular matrix remodeling, tumor metastasis, hyaluronan signaling, and inflammatory disease modeling, particularly in the context of drug resistance. They also support studies on the mechanistic basis of metastatic dissemination, hyaluronan-CD44 interactions in chemoresistance, and screening of compounds targeting matrix-dependent pathways. For further information, please contact Ascent Research.
