The CASP4 Knockout MES-OV Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population generated from the MES-OV human ovarian cancer cell line. This product provides a heterogeneous pool of cells with disrupted CASP4 expression, avoiding clonal selection artifacts and offering a robust loss-of-function model. CASP4 encodes caspase-4, an inflammatory caspase that detects cytosolic lipopolysaccharide (LPS) and triggers pyroptosis and non-canonical inflammasome activation. By deleting CASP4, this model facilitates the study of caspase-4-dependent signaling and its biological consequences.
MES-OV is an epithelial cell line derived from a human ovarian endometrioid carcinoma, a subtype of ovarian cancer with distinct molecular features. These cells retain tumorigenic properties and inflammatory signaling capacities, making them an appropriate host for investigating how innate immune pathways intersect with ovarian cancer biology. The use of an endometrioid carcinoma line allows researchers to examine CASP4 function within a disease-relevant genetic and phenotypic context.
Caspase-4 acts as an intracellular LPS receptor. LPS binding induces oligomerization and activation, resulting in cleavage of gasdermin D (GSDMD) to trigger pyroptosis. The N-terminal GSDMD fragments form membrane pores that also facilitate K+ efflux, indirectly activating the NLRP3 inflammasome and promoting maturation of IL-1?? and IL-18. CASP4 expression is upregulated by type I interferons (IFN-??/??) via the transcription factor IRF1, linking its function to inflammatory cytokine responses. Additionally, CASP4 interacts with the canonical inflammasome components caspase-1 and ASC, mediating crosstalk between pyroptosis and inflammasome pathways.
In ovarian endometrioid carcinoma cells, CASP4 disruption allows dissection of LPS-driven pyroptosis and cytokine release in a clinically relevant setting. Ovarian cancers often exhibit dysregulated inflammatory networks, and bacterial products can access the peritoneal cavity, potentially engaging CASP4. This knockout model enables researchers to determine whether CASP4-mediated inflammation promotes tumor progression or enhances anti-tumor immunity. It also provides a platform to assess CASP4’s contribution to chemoresistance or immune evasion in ovarian cancer.
These polyclonal knockout cells are suitable for LPS stimulation experiments to measure pyroptosis via LDH release, assess GSDMD cleavage by Western blot, and quantify secreted IL-1??/IL-18 by ELISA. The model supports qPCR analysis of inflammasome gene expression and flow cytometric detection of cell death. It is also valuable for drug screening targeting CASP4 or downstream effectors in inflammatory diseases such as sepsis and inflammatory bowel disease. For additional information, please contact Ascent Research.
