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Effects of antioxidant enzyme overexpression on the invasive phenotype of hamster cheek pouch carcinoma cells

Lam, Ernest WN and Zwacka, Ralf and Seftor, Elizabeth A and Nieva, Daniel RC and Davidson, Beverly L and Engelhardt, John F and Hendrix, Mary JC and Oberley, Larry W (1999) 'Effects of antioxidant enzyme overexpression on the invasive phenotype of hamster cheek pouch carcinoma cells.' Free Radical Biology and Medicine, 27 (5-6). pp. 572-579. ISSN 0891-5849

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Abstract

To examine the role of reactive oxygen species on the invasive phenotype of cancer cells, we overexpressed manganese- and copper-zinc-containing superoxide dismutases (MnSOD, CuZnSOD) and catalase (Cat) in hamster cheek pouch carcinoma (HCPC-1) cells in vitro using adenoviral vector-mediated gene transfer. Hamster cheek pouch carcinoma cells were transduced with these adenoviral vector constructs alone, or in combination, at concentrations [i.e., multiplicity of infectivity (MOI)] of 100 MOI each. The Escherichia coli β-galactosidase reporter construct was used as a control virus. Protein expression was examined by Western blot analysis and enzymatic activities were measured using spectrophotometry. To observe the effects of transgene overexpression on in vitro tumor cell invasion, we used the membrane invasion culture system, an accurate and reliable method for examining tumor cell invasion, in vitro. This assay measures the ability of tumor cells to invade a basement membrane matrix consisting of type IV collagen, laminin, and gelatin. MnSOD overexpression resulted in a 50% increase in HCPC-1 cell invasiveness (p < .001); co-overexpression of MnSOD with Cat partially inhibited this effect (p < .05). Moreover, co-overexpression of both SODs resulted in a significant increase in invasiveness compared with the parental HCPC-1 cells (p < .05). These changes could not be correlated with the 72 kDa collagenase IV or stromolysin activities using zymography, or the downregulation of the adhesion molecules E-cadherin or the α4 subunit of the α4β1 integrin. These results suggest that hydrogen peroxide may play a role in the process of tumor cell invasion, but that the process does not rely on changes in matrix metalloproteinase activity in the cells, or the expression of cell adhesion molecules. Copyright (C) 1999 Elsevier Science Inc.

Item Type: Article
Uncontrolled Keywords: Tumor Cells, Cultured; Animals; Humans; Adenoviridae; Neoplasm Invasiveness; Metalloendopeptidases; Catalase; Superoxide Dismutase; Cell Adhesion Molecules; Transduction, Genetic; Gene Expression Regulation, Enzymologic; Phenotype; Cricetinae
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 04 Jul 2017 11:21
Last Modified: 15 Jan 2022 00:55
URI: http://repository.essex.ac.uk/id/eprint/8344

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