The HS3ST1 Knockout PaTu 8988t Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population derived from the human PaTu 8988t pancreatic ductal adenocarcinoma line, offering a heterogeneous loss-of-function model for HS3ST1. This product enables investigation of heparan sulfate 3-O-sulfotransferase 1 function without the selection biases of clonal lines, making it suitable for studies requiring representative gene disruption across a cell pool.
The parental PaTu 8988t cells originate from a liver metastasis of human pancreatic ductal adenocarcinoma and carry KRAS G12V and TP53 mutations, key genetic drivers of aggressive tumor behavior. This metastatic background provides a clinically relevant context for examining gene functions in pancreatic cancer progression, drug response, and metastatic dissemination.
HS3ST1 catalyzes 3-O-sulfation of glucosamine residues in heparan sulfate using PAPS as a sulfate donor. This modification creates binding motifs for antithrombin III, enhancing its anticoagulant activity, and for growth factors including FGF2, HGF, and VEGF, thereby facilitating signaling through FGFR1, MET, and VEGFR, respectively. Thus, HS3ST1 is a critical regulator of both coagulation and growth factor-mediated pathways, acting within the heparan sulfate proteoglycan network.
In PaTu 8988t cells, HS3ST1 disruption is expected to alter heparan sulfate sulfation patterns, impacting FGF2/FGFR1 proliferative signaling, HGF/MET-driven invasion, and VEGF-mediated angiogenesis. Loss of antithrombin III binding sites may also perturb local coagulation. This knockout model permits dissection of how HS3ST1-mediated sulfation contributes to the aggressive phenotype of metastatic pancreatic cancer, including tumor-microenvironment interactions.
These polyclonal knockout cells support diverse research applications, including heparan sulfate disaccharide analysis by HPLC-MS, sulfotransferase activity profiling, and antithrombin binding assays. Functional consequences on signaling can be assessed via phospho-ERK western blotting for FGF2 responsiveness, and metastatic behavior studied through migration and invasion assays. Additional applications encompass viral entry mechanism studies and transcriptomic analyses using RNA-seq. For further information, contact Ascent Research.
