The HPSE Knouckout SK-HEP-1 Polyclonal Cells consist of a CRISPR/Cas9-edited polyclonal knockout cell population derived from SK-HEP-1, a human liver adenocarcinoma cell line. The HPSE gene is disrupted via CRISPR/Cas9-mediated gene targeting, generating a heterogeneous pool of knockout cells that collectively ablate heparanase function. This polyclonal format offers a cost-effective and physiologically relevant model for loss-of-function investigations, avoiding clonal artifacts while maintaining functional diversity.
SK-HEP-1 cells were originally isolated from the ascites of a patient with liver adenocarcinoma and exhibit notable endothelial-like properties, including the ability to form capillary-like tubes and express endothelial markers. They are widely employed in cancer research to model tumor cell invasion, angiogenesis, and the metastatic cascade. Their mesenchymal/epithelial plasticity makes them particularly useful for studying how tumor cells interact with the extracellular matrix and adapt to microenvironmental cues.
HPSE encodes heparanase, the only known mammalian endoglycosidase capable of cleaving heparan sulfate chains of proteoglycans such as syndecan-1. This enzymatic activity liberates sequestered growth factors including FGF-2, VEGF, HGF, HB-EGF, and PDGF, which then bind their cognate receptors (e.g., FGFR, VEGFR) and trigger downstream phosphorylation of ERK1/2 and Akt. Upstream, HPSE expression is induced by TNF-??, Egr1, Ets1, and p53, and is fine-tuned by MAPK signaling. Heparanase also forms complexes with integrin ??V??3, enhancing cell adhesion and migration signaling. By remodeling the tumor microenvironment, heparanase promotes proliferation, angiogenesis, and invasive behavior.
In the context of SK-HEP-1 liver adenocarcinoma, HPSE knockout disrupts the heparanase-mediated release of matrix-bound growth factors, thereby altering autocrine and paracrine signaling loops that sustain the endothelial-like phenotype. The polyclonal knockout population enables researchers to assess how loss of heparanase impacts tube formation, cellular motility, and the activation of downstream effectors such as MMP-9 and phospho-ERK. This model is particularly valuable for dissecting the contribution of heparanase to the acquisition of invasive properties and the crosstalk between tumor cells and the surrounding stroma in hepatic cancer.
Typical experiments with these polyclonal knockout cells encompass Transwell migration and invasion assays, tube formation assays for angiogenesis, and heparanase activity measurements. Immunofluorescence can visualize changes in heparan sulfate distribution, while Western blotting and RT-qPCR quantify downstream effectors like phospho-ERK, MMP-9, and released growth factors such as FGF-2 and VEGF. The cells are also suitable for testing anti-heparanase therapeutic agents and exploring pathway crosstalk. For additional technical information or to request a quote, please contact Ascent Research.
