Effects of heme oxygenase-1 on induction and development of chemically induced squamous cell carcinoma in mice |
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Authors: | Was Halina Sokolowska Malgorzata Sierpniowska Aleksandra Dominik Paweł Skrzypek Klaudia Lackowska Bozena Pratnicki Antoni Grochot-Przeczek Anna Taha Hevidar Kotlinowski Jerzy Kozakowska Magdalena Mazan Andrzej Nowak Witold Muchova Lucie Vitek Libor Ratajska Anna Dulak Jozef Jozkowicz Alicja |
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Affiliation: | a Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Polandb Department of Biophysics, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, 30-387 Krakow, Polandc Department of Pathology, Oncology Center, Krakow, Polandd Department of Pathological Anatomy, Medical University of Warsaw, Warsaw, Polande Charles University, Prague, Czech Republic |
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Abstract: | Heme oxygenase-1 (HO-1) is an antioxidative and cytoprotective enzyme, which may protect neoplastic cells against anticancer therapies, thereby promoting the progression of growing tumors. Our aim was to investigate the role of HO-1 in cancer induction. Experiments were performed in HO-1+/+, HO-1+/−, and HO-1−/− mice subjected to chemical induction of squamous cell carcinoma with 7,12-dimethylbenz[a]anthracene and phorbol 12-myristate 13-acetate. Measurements of cytoprotective genes in the livers evidenced systemic oxidative stress in the mice of all the HO-1 genotypes. Carcinogen-induced lesions appeared earlier in HO-1−/− and HO-1+/− than in wild-type animals. They also contained much higher concentrations of vascular endothelial growth factor and keratinocyte chemoattractant, but lower levels of tumor necrosis factor-α and interleukin-12. Furthermore, tumors grew much larger in HO-1 knockouts than in the other groups, which was accompanied by an increased rate of animal mortality. However, pathomorphological analysis indicated that HO-1−/− lesions were mainly large but benign papillomas. In contrast, in mice expressing HO-1, most lesions displayed dysplastic features and developed to invasive carcinoma. Thus, HO-1 may protect healthy tissues against carcinogen-induced injury, but in already growing tumors it seems to favor their progression toward more malignant forms. |
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Keywords: | Heme oxygenase-1 Carcinogenesis Squamous cell carcinoma DMBA Inflammation Oxidative stress Free radicals |
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