The DPP9 Knockout NCI-H1299 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the dipeptidyl peptidase 9 (DPP9) gene in human NCI-H1299 cells. This loss-of-function model eliminates DPP9 enzymatic activity, enabling investigation of its roles in peptide trimming, antigen processing, and NLRP1 inflammasome regulation.
The host NCI-H1299 line, derived from a lymph node metastasis of a lung adenocarcinoma in a 43-year-old Caucasian male, is a well-established model for non-small cell lung carcinoma (NSCLC). These epithelial cells recapitulate key aspects of NSCLC biology, including proliferation, metastasis, and drug sensitivity, providing a relevant context for studying lung cancer-related pathways.
DPP9 cleaves N-terminal dipeptides from substrates like neuropeptide Y, GLP-1, and CXCL12, and acts as a key suppressor of the NLRP1 inflammasome by binding and maintaining NLRP1 in an autoinhibited state. Gene disruption disinhibits NLRP1, leading to ASC nucleation, caspase-1 activation, and proteolytic maturation of IL-1?? and IL-18, which can drive pyroptosis. DPP9 also participates in MHC class I antigen processing in concert with TAP and ERAP. It interacts with integrin complexes and DPP8, and is regulated by interferon-gamma and pro-inflammatory cytokines, integrating innate immunity with integrin?CFAK?CSrc-mediated adhesion signaling.
In NCI-H1299 cells, DPP9 knockout is particularly valuable for dissecting the intersection of inflammasome-driven pyroptosis and NSCLC. Loss of DPP9-mediated NLRP1 suppression may sensitize these cells to inflammatory death, providing a model to study how pyroptosis influences tumor survival and immune recognition. Impaired peptide trimming could alter the MHC class I immunopeptidome, potentially affecting tumor immunogenicity, while compromised integrin signaling may reduce cell adhesion and migration, enabling studies of metastatic behavior.
These polyclonal knockout cells support a broad range of assays, including western blotting and RT-qPCR for DPP9, NLRP1, ASC, and IL-1??; NLRP1 inflammasome activation measured by IL-1?? release; peptide substrate cleavage assays; cell adhesion and migration studies; pyroptosis detection via LDH release; and drug sensitivity testing with DPP8/9 inhibitors. For further information, please contact Ascent Research.
