The HS3ST1 Knockout NCI-H1703 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal population with disruption of the HS3ST1 gene, which encodes heparan sulfate 3-O-sulfotransferase 1. This pool of NCI-H1703 cells provides a loss-of-function model for studying the roles of 3-O-sulfated heparan sulfate. The polyclonal format maintains population heterogeneity suitable for bulk phenotypic analyses.
The NCI-H1703 cell line originates from a human lung squamous cell carcinoma from a 54-year-old male smoker and serves as a well-characterized model in non-small cell lung cancer (NSCLC) research. Its KRAS-dependent signaling and relevance to squamous cell carcinoma biology make it ideal for investigating lung cancer mechanisms.
HS3ST1 catalyzes 3-O-sulfation of glucosamine residues in heparan sulfate, generating antithrombin III binding sites and modulating growth factor interactions. It is regulated by the SP1 transcription factor, KRAS signaling, and FGF2 stimulation. Its product enhances antithrombin-mediated inhibition of Factor Xa and thrombin and facilitates formation of FGF2?CFGFR1 and VEGF165?CVEGFR2 complexes. HS3ST1 functions in the Golgi membrane using PAPS as a co-substrate and also interacts with the CXCL12?CCXCR4 pathway.
In NCI-H1703 cells, HS3ST1 knockout is predicted to reduce 3-O-sulfated heparan sulfate, impairing antithrombin binding and coagulation regulation, relevant to cancer-associated thrombosis. It likely attenuates FGF2- and VEGF165-driven signaling, diminishing tumor cell proliferation and angiogenesis. Additionally, these cells serve as a platform to study 3-O-sulfated heparan sulfate roles in viral entry by HSV and SARS-CoV-2 in a lung cancer microenvironment.
Representative assays include RT-qPCR, western blotting, mass spectrometry-based disaccharide analysis, antithrombin binding, and FGF2/VEGF165 signaling measurement. Functional studies such as migration and invasion assays can be performed. These polyclonal knockout cells are suitable for lung cancer signaling, coagulation biology, viral infection models, and heparan sulfate research. For more information, contact Ascent Research.
