Hyperglycemia Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer via Hydrogen Peroxide

• Published in: Oxidative medicine and cellular longevity Vol. 2016; no. 2016; pp. 1 - 9
• Main Authors: Zong, Liang, Jiang, Zhengdong, Chen, Xin, Zhang, Lun, Li, Wei, Ma, Qingyong
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2016; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Animals; Blood Glucose - metabolism; Catalase - pharmacology; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell Proliferation; Development and progression; Dextrose; Diabetes; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - complications; Epithelial-Mesenchymal Transition; Free Radical Scavengers - pharmacology; Glucose; Health aspects; Humans; Hydrogen peroxide; Hydrogen Peroxide - blood; Hyperglycemia; Hypotheses; Liver; Liver cancer; Liver Neoplasms - blood; Liver Neoplasms - secondary; Medical prognosis; Metastasis; Mice, Inbred BALB C; Mice, Nude; Morphology; Motility; Pancreatic cancer; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - complications; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Peritoneal dialysis; Polyethylene glycol; Polyethylene Glycols - pharmacology; Signal Transduction; Stem cells; Streptozocin; Studies; Time Factors; Tumor Burden; Xenograft Model Antitumor Assays; China
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2016/5190314

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.