The HS3ST1 Knockout HT29 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HT29 colorectal adenocarcinoma cell line. This product offers a loss-of-function model for HS3ST1, encoding heparan sulfate 3-O-sulfotransferase 1, achieved through targeted gene disruption without clonal isolation. The polyclonal format ensures a diverse repertoire of genetic alterations, facilitating robust functional studies.
The parental HT29 line, established from a primary colorectal adenocarcinoma of a 44-year-old Caucasian female, carries oncogenic mutations in APC and TP53, making it a standard model for intestinal epithelial biology, cancer progression, and drug absorption research. HT29 cells maintain an epithelial phenotype, forming monolayers suitable for transport and barrier function assays.
HS3ST1 catalyzes the 3-O-sulfation of glucosamine residues in heparan sulfate chains, a modification essential for antithrombin III high-affinity binding and for tuning the activity of heparin-binding growth factors. The enzyme functions downstream of the EXT1/EXT2 copolymerase and sulfotransferases HS2ST and HS6ST, and is transcriptionally regulated by Wnt/??-catenin signaling and cytokines TNF-?? and IL-1??. 3-O-sulfated motifs mediate interactions with antithrombin III, FGF2, VEGF, PDGF, and HGF via heparan sulfate proteoglycans such as syndecans and glypicans. Consequently, HS3ST1 knockout disrupts antithrombin binding and attenuates signaling by these growth factors, including the FGF2-FGFR1 pathway.
In HT29 colorectal cancer cells, ablation of HS3ST1 impairs heparan sulfate-dependent antithrombin III recruitment, potentially altering pericellular coagulation dynamics relevant to tumor thrombosis. Additionally, disrupted growth factor signaling may reduce proliferation, migration, and angiogenesis, as 3-O-sulfation is required for optimal FGF2, VEGF, and PDGF pathway activation. This knockout model thus provides a platform to dissect the role of heparan sulfate fine structure in colorectal adenocarcinoma progression and the tumor microenvironment.
These cells support a wide range of glycobiology and cancer research applications, including heparan sulfate disaccharide analysis by HPLC-MS, antithrombin binding assays, tube formation angiogenesis assays, and migration/invasion studies. The model is also suited for RNA-seq transcriptomic profiling and screening of coagulation or angiogenic modulators. For further information, please contact Ascent Research.
