The ELANE Knockout NCI-H1703 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1703 human lung squamous cell carcinoma line. This product provides a heterogeneous pool of cells with targeted disruption of the ELANE gene, encoding neutrophil elastase. The polyclonal format enables study of ELANE loss-of-function across a diverse genetic background, avoiding clonal artifacts, and is suitable for investigating elastase roles in lung cancer biology and inflammation.
The NCI-H1703 parental line is a well-characterized model of human non-small cell lung carcinoma with squamous differentiation and adherent epithelial morphology. Widely used in lung cancer research, it retains key inflammatory response pathways, making it particularly suited for investigating interactions between neutrophil-derived proteases and tumor progression.
ELANE encodes neutrophil elastase (NE), a serine protease released during neutrophil degranulation. Transcriptionally regulated by CEBPA and SPI1, and induced by G-CSF and IL-8, NE cleaves elastin, collagens, and E-cadherin, thereby modulating ECM and adhesion. It processes pro-IL-1?? and promotes TNF-?? shedding via TACE, linking to NF-??B and inflammasome signaling. NE activates PAR1/2, cleaves TLR4, and is inhibited by SERPINA1, SLPI, and Elafin. Disruption of ELANE thus abrogates these proteolytic events, interrupting pathways involving MMP9, IRAK1, NFKB1, IL1B, and CXCR2, and dampening neutrophil-driven inflammation and remodeling.
In NCI-H1703 cells, ELANE knockout eliminates functional elastase, impairing autocrine or paracrine tumor-promoting mechanisms. Although these cells are not professional neutrophils, elastase acquisition from the microenvironment can foster ECM degradation, MMP activation, and pro-inflammatory cytokine release. This knockout model thus attenuates elastase-dependent signaling, enabling dissection of pathways that fuel tumor cell invasion, proliferation, and interplay with stromal and immune components in the lung cancer niche.
This polyclonal knockout product is suited for exploring ELANE-mediated tumor invasion via Boyden chamber or Matrigel assays, profiling inflammatory cytokines by ELISA/RNA-seq, and screening elastase inhibitors. Co-culture with neutrophils permits evaluation of PAR1 cleavage by flow cytometry and MMP9 activity by zymography. Additional applications include investigating chronic inflammation-driven squamous carcinogenesis, emphysema-to-cancer progression, and EGFR signaling crosstalk. For further information, contact Ascent Research.
