Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue
2022
Аутори:
Kalezić, AnđelikaUdički, Mirjana
Srdić Galić, Biljana
Korać, Aleksandra
Janković, Aleksandra
Korać, Bato
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2022 by the Society for Free Radical Research-Europe
Метаподаци
Приказ свих података о документуАпстракт:
Altered redox homeostasis is recognized as a hallmark of neoplastic transformation. However, data from various in vitro and in vivo studies often show increased or decreased transcriptional and translational levels of antioxidant defense (AD) enzymes. One of the underlying causes for such conflicting reports is cell heterogeneity within the complex tumor microenvironment, especially in breast cancer. To overcome barriers associated with bulk tissue gene and protein expression analysis, we choose an immunohistochemical approach. We cross-examined serial tissue sections of tumor and adipose tissue from premenopausal women with malignant invasive ductal carcinoma and benign fibroadenoma to gain a comprehensive overview of cell-specific AD enzymes expression and localization patterns. At the level of overall tissue architecture, malignant tumor tissue shows significantly higher immunopositivity for copper, zinc- and manganese- superoxide dismutase, catalase, and glutathione peroxidase compared to benign tumor tissue. Generally, AD enzymes are specifically localized in the cytoplasm (copper, zinc superoxide dismutase, catalase, glutathione peroxidase) and mitochondria (manganese superoxide dismutase, glutathione peroxidase) of cancer cells and cancer-associated adipocytes. Detailed analysis of different regions of the tumor tissue revealed significant heterogeneity in the degree of immunopositivity along the axis of tumor center–invasive front–adipose tissue. Clusters of cancer cells at the invasive front of the tumor often show a higher degree of immunopositivity for AD enzymes compared to cancer cells in the center of the tumor mass. Similarly, cancer-associated adipocytes that are in close proximity to cancer cells at the invasive front of the tumor show a higher degree of immunopositivity for AD enzymes compared to adipocytes from distant peritumoral adipose tissue. In conclusion, immunohistochemical approach confirms high AD enzymes expression in breast cancer and further reveals distinct regional mosaicism consistent with cell heterogeneity within the tumor microenvironment. This research was supported by the Science Fund of the Republic of Serbia, #7750238-REFRAME.
Финансирање / пројекти:
- REFRAME - Exploring New Avenues in Breast Cancer Research: Redox and Metabolic Reprogramming of Cancer and Associated Adipose Tissue (RS-ScienceFundRS-Ideje-7750238)
У:
- Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium. Society for Free Radical Research-Europe; 2022. p. 35-6. (Free Radical Biology and Medicine; Vol. 189; Suppl. 1).