title: Pivotal role of oxidative stress in tumor metastasis under diabetic conditions in mice.
abstract: Diabetic patients are reported to have a high incidence and mortality of cancer, but little is known about the linkage. In this study, we investigated whether high oxidative stress is involved in the acceleration of tumor metastasis in diabetic mice. Murine melanoma B16-BL6 cells stably labeled with firefly luciferase (B16-BL6/Luc) were inoculated into the tail vein of streptozotocin (STZ)-treated or untreated mice. A luciferase assay demonstrated that tumor cells were present largely in the lung of untreated mice, whereas large numbers of tumor cells were detected in both the lung and liver of STZ-treated mice. Repeated injections of polyethylene glycol-conjugated catalase (PEG-catalase), a long-circulating derivative, reduced the elevated fasting blood glucose levels and plasma lipoperoxide levels of STZ-treated mice, but had no significant effects on these parameters in untreated mice. In addition, the injections significantly reduced the number of tumor cells in the lung and liver in both untreated and STZ-treated mice. Culture of B16-BL6/Luc cells in medium containing over 45 mg/dl glucose hardly affected the proliferation of the cells, whereas the addition of plasma of STZ-treated mice to the medium significantly increased the number of cells. Plasma samples of STZ-treated mice receiving PEG-catalase exhibited no such effect on proliferation. These findings indicate that a hyperglycemia-induced increase in oxidative stress is involved in the acceleration of tumor metastasis, and the removal of systemic hydrogen peroxide by PEG-catalase can inhibit the progression of diabetic conditions and tumor metastasis in diabetes.
authors.affiliation: Department of Drug Delivery Research, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Ikemura
authors.forename: Makiya
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kusamori
authors.forename: Miho
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002374:Catalase / Q000008:administration & dosage*; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D011092:Polyethylene Glycols / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; C070295:catalase-polyethylene glycol; D011092:Polyethylene Glycols; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D002374:Catalase
keywords: Diabetes; Hyperglycemia; Reactive oxygen species; Tumor metastasis