The HS3ST1 Knockout A2780 Polyclonal Cells product is a CRISPR/Cas9-edited human cell pool featuring disruption of the HS3ST1 gene in the A2780 ovarian carcinoma background. This polyclonal knockout population provides a genetically diverse loss-of-function model for investigating heparan sulfate 3-O-sulfation. The targeted gene disruption abrogates HS3ST1 enzymatic activity, enabling researchers to dissect the roles of 3-O-sulfated motifs in cellular processes without bias from clonal selection.
The A2780 host cell line is an epithelial ovarian carcinoma model derived from an untreated patient. It is widely employed in cancer biology for studying ovarian tumorigenesis, metastasis, and mechanisms of chemoresistance. The cell line retains key signaling networks relevant to ovarian cancer, including those modulated by heparan sulfate proteoglycans, making it a suitable platform for examining the tumor-specific functions of HS3ST1.
HS3ST1 encodes a sulfotransferase that catalyzes the 3-O-sulfation of glucosamine residues in heparan sulfate chains, generating critical binding sites for antithrombin III. This interaction potentiates the anticoagulant activity of antithrombin III, which inhibits thrombin and factor Xa. Beyond coagulation, HS3ST1-modulated heparan sulfate regulates growth factor signaling: it mediates FGF2 binding and FGFR1 activation, influencing downstream FRS2?CMAPK cascades, and facilitates VEGF165 interactions that promote angiogenesis. Upstream regulators such as FGF2, TGFB1, and WNT3A can modulate HS3ST1 expression, while HSV-1 glycoprotein D exploits 3-O-sulfated motifs for viral entry. Thus, HS3ST1 serves as a node connecting extracellular signals to cellular responses in proliferation, migration, and infection.
Disruption of HS3ST1 in A2780 cells creates a powerful tool for dissecting how altered heparan sulfation impacts ovarian carcinoma pathophysiology. Loss of 3-O-sulfation is expected to perturb antithrombin III binding and downstream coagulation, though its primary relevance in cancer links to growth factor signaling. Impaired FGF2 and VEGF165 interactions may attenuate MAPK-driven proliferation and angiogenic signaling, potentially affecting tumor growth and drug resistance. Moreover, compromised viral entry mechanics allow investigation of HS3ST1 as a herpes simplex virus-1 receptor, while changes in cell adhesion and invasion can be studied via syndecans and glypicans. This model enables exploration of the crosstalk between the coagulation cascade and oncogenic pathways.
This knockout cell pool is suited for a range of functional assays. Researchers can quantify heparan sulfate disaccharide composition by HPLC-MS, assess antithrombin III binding with ELISA, and measure FGF2 signaling via phospho-FGFR1 western blotting. Cell-based studies include proliferation (MTS), migration/invasion (Transwell), and HSV-1 entry assays. Transcriptomic analysis by RNA-seq can reveal downstream targets regulated by HS3ST1-dependent sulfation. For inquiries or technical assistance, please contact Ascent Research.
