The DPP9 Knockout MES-OV Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the MES-OV human ovarian cancer cell line. This product features targeted disruption of the DPP9 gene, generating a heterogeneous pool of cells with loss-of-function mutations across the DPP9 locus. As a polyclonal knockout pool, it retains genetic diversity while ensuring robust abrogation of DPP9 expression, making it a versatile tool for pooled functional studies without the biases of clonal variation.
The parental MES-OV cell line is a well-characterized model of human endometrioid ovarian carcinoma, a distinct subtype of epithelial ovarian cancer. MES-OV cells exhibit molecular and phenotypic features consistent with endometrioid histology, including relevant oncogenic signaling pathways and an epithelial lineage. This cell line provides a clinically relevant context for investigating tumor biology, particularly the interplay between cancer cell signaling and inflammatory responses within the ovarian tumor microenvironment.
DPP9 encodes dipeptidyl peptidase 9, a serine protease that negatively regulates the NLRP1 inflammasome. DPP9 cleaves and inactivates NLRP1 under homeostatic conditions, preventing spontaneous inflammasome assembly. Upon DPP9 loss, as achieved in these knockout cells, NLRP1 is stabilized and recruits ASC and caspase-1 to form the inflammasome complex. This leads to caspase-1-mediated cleavage of pro-IL-1?? and pro-IL-18 into their mature forms and triggers pyroptosis via gasdermin D (GSDMD) pore formation. Upstream signals, including inflammatory cytokines such as TNF-?? and IL-1??, and cellular stress signals modulate this pathway, while downstream targets include NLRP1, pro-inflammatory cytokines, and chemokines. DPP9 also interacts with CARD8 and ASC, further expanding its role in inflammasome regulation and immune signaling.
In the context of endometrioid ovarian carcinoma, the DPP9 knockout MES-OV model offers a unique platform to dissect how inflammasome dysregulation influences tumor growth, immune evasion, and therapy response. Aberrant NLRP1 inflammasome activation has been implicated in inflammatory disorders and may contribute to the inflammatory milieu of ovarian tumors. By engineering DPP9 loss in MES-OV cells, researchers can examine the consequences of chronic pyroptotic signaling, altered cytokine secretion, and crosstalk with adaptive immune pathways, providing insights into both tumor-intrinsic and microenvironmental mechanisms.
These polyclonal DPP9 knockout cells are ideal for a broad range of applications, including functional genomics to dissect DPP9-dependent pathways in ovarian cancer, mechanistic studies of NLRP1 inflammasome regulation, and drug target validation for small-molecule DPP9 inhibitors. Representative assays include western blotting for DPP9 and cleaved caspase-1, ELISA for IL-1?? and IL-18 secretion, LDH release assays to quantify pyroptosis, cell viability assessments, RNA-sequencing for transcriptomic profiling, and co-immunoprecipitation to examine DPP9?CNLRP1 interactions. The polyclonal nature reduces selection-based artifacts and allows robust pooled analyses. For further details, please contact Ascent Research.
