Evaluating Tumor-Associated Activity of Extracellular Sulfatase by Analyzing Naturally Occurring Substrate in Tumor Microenvironment of Hepatocellular Carcinoma

The progress of cancer is intimately connected with the activity of the extracellular matrix (ECM) enzymes. To evaluate the promoting effect of these enzymes on tumor development in a pathological biocontext, we propose in this work to analyze their natural substrates in the ECM. This strategy is demonstrated by studying heparan sulfate (HS), the substrate of ECM sulfatase, in the development of hepatocellular carcinoma (HCC). An assay is designed to study the abundance and sulfation of HS and to evaluate the interactions between HS and the growth factors, such as fibroblast growth factor 2 (FGF2). Peptides derived from the amyloid peptide and various growth factors are employed to detect HS and evaluate their affinity toward the growth factors, whereas the ruthenium polypyridyl complex is taken as a photocatalyst to achieve a more sensitive signal readout. Applying this method to HepG2 cells, correlated changes between the activity of sulfatase 2 in regulating FGF2-induced cell proliferation and the abun...