This product comprises a CRISPR/Cas9-edited polyclonal knockout cell population targeting the HPSE gene in NCI-H1975 human lung adenocarcinoma cells. The polyclonal format maintains genetic diversity while achieving functional gene disruption, providing a robust loss-of-function model that avoids clonal selection biases. It is suitable for investigating heparanase-dependent cellular processes.
The NCI-H1975 cell line is an epithelial model derived from a patient with non-small cell lung cancer (NSCLC). It is widely used to study tumor progression, drug resistance, and metastatic dissemination, in part due to its well-characterized mutations, including EGFR T790M and PIK3CA alterations. This background provides a disease-relevant context for examining HPSE function.
HPSE encodes heparanase, an endo-??-D-glucuronidase that cleaves heparan sulfate chains of proteoglycans in the extracellular matrix and basement membrane. This cleavage liberates sequestered growth factors, notably VEGF, FGF-2, and HGF, which bind to VEGFR and FGFR and activate downstream kinases ERK, Akt, and Src. Heparanase expression is regulated by transcription factors AP-1, NF-??B, and EGR1, and requires proteolytic processing by cathepsin L for activity. It also interacts with cell-surface proteoglycans such as syndecans and glypicans. Through these mechanisms, HPSE orchestrates extracellular matrix remodeling, angiogenesis, and cell invasion.
In NCI-H1975 lung adenocarcinoma cells, HPSE knockout attenuates heparan sulfate degradation and reduces the release of pro-angiogenic and pro-migratory factors. This disruption impairs signaling downstream of receptors like EGFR and MET, which are frequently hyperactivated in NSCLC. The model thus enables precise dissection of HPSE-mediated contributions to tumor invasion, matrix remodeling, and growth factor-dependent proliferation, providing a platform for studying the tumor microenvironment in lung cancer.
These polyclonal HPSE knockout cells are ideal for a range of applications, including migration and invasion assays to evaluate metastatic capacity, heparan sulfate degradation assays to measure enzymatic activity, and ELISA for quantifying secreted VEGF and FGF-2. Additional uses include phospho-signaling analysis of the ERK and Akt pathways, RT-qPCR or western blotting for gene expression validation, and co-culture studies to examine tumor?Cstroma interactions. This product is valuable for cancer progression research, metastasis studies, extracellular matrix analysis, angiogenesis assays, and drug resistance investigations. For further technical information and support, please contact Ascent Research.
