title: Hyperglycemia Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer via Hydrogen Peroxide.
abstract: Diabetes mellitus (DM) and pancreatic cancer are intimately related, as approximately 85% of patients diagnosed with pancreatic cancer have impaired glucose tolerance or even DM. Our previous studies have indicated that high glucose could promote the invasive and migratory abilities of pancreatic cancer cells. We therefore explored the underlying mechanism that hyperglycemia modulates the metastatic potential of pancreatic cancer. Our data showed that streptozotocin- (STZ-) treated diabetic nude mice exhibit larger tumor size than that of the euglycemic mice. The number of nude mice that develop liver metastasis or ascites is much more in the STZ-treated group than that in the euglycemic group. Hyperglycemic mice contain a higher plasma H2O2-level than that from euglycemic mice. The injection of polyethylene glycol-conjugated catalase (PEG-CAT), an H2O2 scavenger, may reverse hyperglycemia-induced tumor metastasis. In addition, hyperglycemia could also modulate the expression of epithelial-mesenchymal transition- (EMT-) related factors in pancreatic tumor tissues, as the E-cadherin level is decreased and the expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail is strongly increased. The injection of PEG-CAT could also reverse hyperglycemia-induced EMT. These results suggest that the association between hyperglycemia and poor prognosis of pancreatic cancer can be attributed to the alterations of EMT through the production of hydrogen peroxide.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Wei
authors.identifier: 0000-0001-5701-3230
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Lun
authors.identifier: 0000-0003-1936-3971
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Xin
authors.identifier: 0000-0003-0509-7510
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Liang
authors.identifier: 0000-0002-3330-4735
authors.initials: L
authors.lastname: Zong
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Qingyong
authors.identifier: 0000-0001-8977-320X
authors.initials: Q
authors.lastname: Ma
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002374:Catalase / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000139:chemically induced / Q000150:complications; D058750:Epithelial-Mesenchymal Transition; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood / Q000556:secondary; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D011092:Polyethylene Glycols / Q000494:pharmacology; D015398:Signal Transduction; D013311:Streptozocin; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D001786:Blood Glucose; D016166:Free Radical Scavengers; C070295:catalase-polyethylene glycol; D011092:Polyethylene Glycols; D013311:Streptozocin; D006861:Hydrogen Peroxide; D002374:Catalase