title: Evaluating Tumor-Associated Activity of Extracellular Sulfatase by Analyzing Naturally Occurring Substrate in Tumor Microenvironment of Hepatocellular Carcinoma.
abstract: 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 abundance, degree of sulfation, and growth factor binding of HS can be observed. This method has also been applied to analyze clinical tissue samples of HCC. The results may suggest tumor-progress-related alterations in the above-studied biochemical features of HS. These results may point to the prospect of using this method to facilitate the diagnosis and prognosis of HCC in the future.
authors.affiliation: Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing 210008, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, Department of Biochemistry, Nanjing University , Nanjing 210093, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University , Nanjing 210011, China.
authors.forename: Yucai
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing 210008, China.
authors.forename: Yitao
authors.identifier: 0000-0003-2599-1499
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University , Nanjing 210011, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, Department of Biochemistry, Nanjing University , Nanjing 210093, China.|Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University , Shanghai 200444, China.
authors.forename: Genxi
authors.initials: G
authors.lastname: Li
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D056945:Hep G2 Cells; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000378:metabolism; D008958:Models, Molecular; D013379:Substrate Specificity; D013429:Sulfatases; D015238:Sulfotransferases / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D013429:Sulfatases; D015238:Sulfotransferases; C470792:SULF2 protein, human