REFRAME - Exploring New Avenues in Breast Cancer Research: Redox and Metabolic Reprogramming of Cancer and Associated Adipose Tissue

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REFRAME - Exploring New Avenues in Breast Cancer Research: Redox and Metabolic Reprogramming of Cancer and Associated Adipose Tissue (en)
Authors

Publications

Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue

Zakić, Tamara; Kalezić, Anđelika; Drvendžija, Zorka; Udicki, Mirjana; Ivković Kapicl, Tatjana; Srdić Galić, Biljana; Korać, Aleksandra; Janković, Aleksandra; Korać, Bato

(Basel: MDPI, 2024)

TY  - JOUR
AU  - Zakić, Tamara
AU  - Kalezić, Anđelika
AU  - Drvendžija, Zorka
AU  - Udicki, Mirjana
AU  - Ivković Kapicl, Tatjana
AU  - Srdić Galić, Biljana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6528
AB  - The close cooperation between breast cancer and cancer-associated adipose tissue (CAAT) shapes the malignant phenotype, but the role of mitochondrial metabolic reprogramming and obesity in breast cancer remains undecided, especially in premenopausal women. Here, we examined mitochondrial metabolic dynamics in paired biopsies of malignant versus benign breast tumor tissue and CAAT in normal-weight and overweight/obese premenopausal women. Lower protein level of pyruvate dehydrogenase and citrate synthase in malignant tumor tissue indicated decreased carbon flux from glucose into the Krebs cycle, whereas the trend was just the opposite in malignant CAAT. Simultaneously, stimulated lipolysis in CAAT of obese women was followed by upregulated β-oxidation, as well as fatty acid synthesis enzymes in both tumor tissue and CAAT of women with malignant tumors, corroborating their physical association. Further, protein level of electron transport chain complexes was generally increased in tumor tissue and CAAT from women with malignant tumors, respective to obesity. Preserved mitochondrial structure in malignant tumor tissue was also observed. However, mitochondrial DNA copy number and protein levels of PGC-1α were dependent on both malignancy and obesity in tumor tissue and CAAT. In conclusion, metabolic cooperation between breast cancer and CAAT in premenopausal women involves obesity-related, synchronized changes in mitochondrial metabolism.
PB  - Basel: MDPI
T2  - Cells
T1  - Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue
IS  - 2
VL  - 13
DO  - 10.3390/cells13020155
SP  - 155
ER  - 
@article{
author = "Zakić, Tamara and Kalezić, Anđelika and Drvendžija, Zorka and Udicki, Mirjana and Ivković Kapicl, Tatjana and Srdić Galić, Biljana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2024",
abstract = "The close cooperation between breast cancer and cancer-associated adipose tissue (CAAT) shapes the malignant phenotype, but the role of mitochondrial metabolic reprogramming and obesity in breast cancer remains undecided, especially in premenopausal women. Here, we examined mitochondrial metabolic dynamics in paired biopsies of malignant versus benign breast tumor tissue and CAAT in normal-weight and overweight/obese premenopausal women. Lower protein level of pyruvate dehydrogenase and citrate synthase in malignant tumor tissue indicated decreased carbon flux from glucose into the Krebs cycle, whereas the trend was just the opposite in malignant CAAT. Simultaneously, stimulated lipolysis in CAAT of obese women was followed by upregulated β-oxidation, as well as fatty acid synthesis enzymes in both tumor tissue and CAAT of women with malignant tumors, corroborating their physical association. Further, protein level of electron transport chain complexes was generally increased in tumor tissue and CAAT from women with malignant tumors, respective to obesity. Preserved mitochondrial structure in malignant tumor tissue was also observed. However, mitochondrial DNA copy number and protein levels of PGC-1α were dependent on both malignancy and obesity in tumor tissue and CAAT. In conclusion, metabolic cooperation between breast cancer and CAAT in premenopausal women involves obesity-related, synchronized changes in mitochondrial metabolism.",
publisher = "Basel: MDPI",
journal = "Cells",
title = "Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue",
number = "2",
volume = "13",
doi = "10.3390/cells13020155",
pages = "155"
}
Zakić, T., Kalezić, A., Drvendžija, Z., Udicki, M., Ivković Kapicl, T., Srdić Galić, B., Korać, A., Janković, A.,& Korać, B.. (2024). Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue. in Cells
Basel: MDPI., 13(2), 155.
https://doi.org/10.3390/cells13020155
Zakić T, Kalezić A, Drvendžija Z, Udicki M, Ivković Kapicl T, Srdić Galić B, Korać A, Janković A, Korać B. Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue. in Cells. 2024;13(2):155.
doi:10.3390/cells13020155 .
Zakić, Tamara, Kalezić, Anđelika, Drvendžija, Zorka, Udicki, Mirjana, Ivković Kapicl, Tatjana, Srdić Galić, Biljana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue" in Cells, 13, no. 2 (2024):155,
https://doi.org/10.3390/cells13020155 . .

The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2

Zakić, Tamara; Budnar-Šoškić, Marta; Stojanović, Sara; Janković, Aleksandra; Korać, Aleksandra; Peković-Vaughan, Vanja; Korać, Bato

(Elsevier, 2023)

TY  - CONF
AU  - Zakić, Tamara
AU  - Budnar-Šoškić, Marta
AU  - Stojanović, Sara
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Peković-Vaughan, Vanja
AU  - Korać, Bato
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6527
AB  - The precise regulatory mechanisms of interscapular brown adipose tissue (IBAT) thermogenesis are not fully elucidated, especially those in relation to Nuclear factor erythroid 2–related factor 2 (Nrf2). We have recently shown that mice lacking functional Nrf2 (Nrf2KO) at room temperature (RT) depict thermogenic IBAT activity at the structural level. However, gene and protein expression of the main IBAT thermogenic marker uncoupling protein 1 (UCP1), and other redox-metabolic functional parameters, did not align with this apparent thermogenic activation. Here, we investigated the functional activation of IBAT in wild-type (WT) and Nrf2KO mice maintained at RT (24±1°C) or after cold acclimation (45 days, 4±1°C). We performed immunogold labelling of Nrf2 and its closely related transcription factors Nrf1, Nrf3, and nuclear respiratory factor 1 (NRF1) to determine their spatial expression patterns. Next, we measured succinate-based mitochondrial respiration as an indicator of IBAT mitochondrial oxidative function and uncoupling capacity. Electron microscopy confirmed that Nrf2KO mice at RT had the same ultrastructural characteristics as cold-exposed mice, indicating IBAT thermogenic activity. This was associated with increased mitochondrial immunogold reaction of the above redox-sensitive transcription factors indicating their activation in Nrf2KO mice at RT. In contrast to such activated phenotype, respirometry results showed that Nrf2KO mice at RT had no uncoupling activity compared to cold-exposed WT mice. Furthermore, similar respiratory pattern was observed in Nrf2KO mice acclimated to cold, regardless of increased UCP1 expression. These results demonstrate that despite the (ultra)structural recruitment of IBAT in Nrf2KO mice at RT and after cold acclimation, Nrf2 is essential for the full functional thermogenic activation of IBAT and the lack of functional Nrf2 could not be compensated with Nrf1, Nrf3, and NRF1.
PB  - Elsevier
C3  - Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
T1  - The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2
DO  - 10.1016/j.freeradbiomed.2023.03.109
SP  - 25
ER  - 
@conference{
author = "Zakić, Tamara and Budnar-Šoškić, Marta and Stojanović, Sara and Janković, Aleksandra and Korać, Aleksandra and Peković-Vaughan, Vanja and Korać, Bato",
year = "2023",
abstract = "The precise regulatory mechanisms of interscapular brown adipose tissue (IBAT) thermogenesis are not fully elucidated, especially those in relation to Nuclear factor erythroid 2–related factor 2 (Nrf2). We have recently shown that mice lacking functional Nrf2 (Nrf2KO) at room temperature (RT) depict thermogenic IBAT activity at the structural level. However, gene and protein expression of the main IBAT thermogenic marker uncoupling protein 1 (UCP1), and other redox-metabolic functional parameters, did not align with this apparent thermogenic activation. Here, we investigated the functional activation of IBAT in wild-type (WT) and Nrf2KO mice maintained at RT (24±1°C) or after cold acclimation (45 days, 4±1°C). We performed immunogold labelling of Nrf2 and its closely related transcription factors Nrf1, Nrf3, and nuclear respiratory factor 1 (NRF1) to determine their spatial expression patterns. Next, we measured succinate-based mitochondrial respiration as an indicator of IBAT mitochondrial oxidative function and uncoupling capacity. Electron microscopy confirmed that Nrf2KO mice at RT had the same ultrastructural characteristics as cold-exposed mice, indicating IBAT thermogenic activity. This was associated with increased mitochondrial immunogold reaction of the above redox-sensitive transcription factors indicating their activation in Nrf2KO mice at RT. In contrast to such activated phenotype, respirometry results showed that Nrf2KO mice at RT had no uncoupling activity compared to cold-exposed WT mice. Furthermore, similar respiratory pattern was observed in Nrf2KO mice acclimated to cold, regardless of increased UCP1 expression. These results demonstrate that despite the (ultra)structural recruitment of IBAT in Nrf2KO mice at RT and after cold acclimation, Nrf2 is essential for the full functional thermogenic activation of IBAT and the lack of functional Nrf2 could not be compensated with Nrf1, Nrf3, and NRF1.",
publisher = "Elsevier",
journal = "Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria",
title = "The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2",
doi = "10.1016/j.freeradbiomed.2023.03.109",
pages = "25"
}
Zakić, T., Budnar-Šoškić, M., Stojanović, S., Janković, A., Korać, A., Peković-Vaughan, V.,& Korać, B.. (2023). The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
Elsevier., 25.
https://doi.org/10.1016/j.freeradbiomed.2023.03.109
Zakić T, Budnar-Šoškić M, Stojanović S, Janković A, Korać A, Peković-Vaughan V, Korać B. The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria. 2023;:25.
doi:10.1016/j.freeradbiomed.2023.03.109 .
Zakić, Tamara, Budnar-Šoškić, Marta, Stojanović, Sara, Janković, Aleksandra, Korać, Aleksandra, Peković-Vaughan, Vanja, Korać, Bato, "The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2" in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria (2023):25,
https://doi.org/10.1016/j.freeradbiomed.2023.03.109 . .

Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue

Zakić, Tamara; Peković-Vaughan, Vanja; Čvoro, Aleksandra; Korać, Aleksandra; Janković, Aleksandra; Korać, Bato

(John Wiley, 2023)

TY  - JOUR
AU  - Zakić, Tamara
AU  - Peković-Vaughan, Vanja
AU  - Čvoro, Aleksandra
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6519
AB  - Redox and metabolic processes are tightly coupled in both physiological and pathological conditions. In cancer, their integration occurs at multiple levels and is characterized by synchronized reprogramming both in the tumor tissue and its specific but heterogeneous microenvironment. In breast cancer, the principal microenvironment is the cancer-associated adipose tissue (CAAT). Understanding how the redox-metabolic reprogramming becomes coordinated in human breast cancer is imperative both for cancer prevention and for the establishment of new therapeutic approaches. This review aims to provide an overview of the current knowledge of the redox profiles and regulation of intermediary metabolism in breast cancer while considering the tumor and CAAT of breast cancer as a unique Warburg's pseudo-organ. As cancer is now recognized as a systemic metabolic disease, we have paid particular attention to the cell-specific redox-metabolic reprogramming and the roles of estrogen receptors and circadian rhythms, as well as their crosstalk in the development, growth, progression, and prognosis of breast cancer.
PB  - John Wiley
T2  - FEBS Letters
T1  - Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue
DO  - 10.1002/1873-3468.14794
ER  - 
@article{
author = "Zakić, Tamara and Peković-Vaughan, Vanja and Čvoro, Aleksandra and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2023",
abstract = "Redox and metabolic processes are tightly coupled in both physiological and pathological conditions. In cancer, their integration occurs at multiple levels and is characterized by synchronized reprogramming both in the tumor tissue and its specific but heterogeneous microenvironment. In breast cancer, the principal microenvironment is the cancer-associated adipose tissue (CAAT). Understanding how the redox-metabolic reprogramming becomes coordinated in human breast cancer is imperative both for cancer prevention and for the establishment of new therapeutic approaches. This review aims to provide an overview of the current knowledge of the redox profiles and regulation of intermediary metabolism in breast cancer while considering the tumor and CAAT of breast cancer as a unique Warburg's pseudo-organ. As cancer is now recognized as a systemic metabolic disease, we have paid particular attention to the cell-specific redox-metabolic reprogramming and the roles of estrogen receptors and circadian rhythms, as well as their crosstalk in the development, growth, progression, and prognosis of breast cancer.",
publisher = "John Wiley",
journal = "FEBS Letters",
title = "Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue",
doi = "10.1002/1873-3468.14794"
}
Zakić, T., Peković-Vaughan, V., Čvoro, A., Korać, A., Janković, A.,& Korać, B.. (2023). Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue. in FEBS Letters
John Wiley..
https://doi.org/10.1002/1873-3468.14794
Zakić T, Peković-Vaughan V, Čvoro A, Korać A, Janković A, Korać B. Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue. in FEBS Letters. 2023;.
doi:10.1002/1873-3468.14794 .
Zakić, Tamara, Peković-Vaughan, Vanja, Čvoro, Aleksandra, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue" in FEBS Letters (2023),
https://doi.org/10.1002/1873-3468.14794 . .
1
2
1

Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation

Zakić, Tamara; Stojanović, Sara; Janković, Aleksandra; Korać, Aleksandra; Peković‐Vaughan, Vanja; Korać, Bato

(2022)

TY  - JOUR
AU  - Zakić, Tamara
AU  - Stojanović, Sara
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Peković‐Vaughan, Vanja
AU  - Korać, Bato
PY  - 2022
UR  - https://onlinelibrary.wiley.com/doi/10.1002/biof.1931
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5385
AB  - Adaptive responses to environmental and physiological challenges, including exposure to low environmental temperature, require extensive structural, redox, and metabolic reprogramming. Detailed molecular mechanisms of such processes in the skin are lacking, especially the role of nuclear factor erythroid 2-related factor 2 (Nrf2) and other closely related redox-sensitive transcription factors Nrf1, Nrf3, and nuclear respiratory factor (NRF1). To investigate the role of Nrf2, we examined redox and metabolic responses in the skin of wild-type (WT) mice and mice lacking functional Nrf2 (Nrf2 KO) at room (RT, 24 ± 1°C) and cold (4 ± 1°C) temperature. Our results demonstrate distinct expression profiles of major enzymes involved in antioxidant defense and key metabolic and mitochondrial pathways in the skin, depending on the functional Nrf2 and/or cold stimulus. Nrf2 KO mice at RT displayed profound alterations in redox, mitochondrial and metabolic responses, generally akin to cold-induced skin responses in WT mice. Immunohistochemical analyses of skin cell compartments (keratinocytes, fibroblasts, hair follicle, and sebaceous gland) and spatial locations (nucleus and cytoplasm) revealed synergistic interactions between members of the Nrf transcription factor family as part of redox-metabolic reprogramming in WT mice upon cold acclimation. In contrast, Nrf2 KO mice at RT showed loss of NRF1 expression and a compensatory activation of Nrf1/Nrf3, which was abolished upon cold, concomitant with blunted redox-metabolic responses. These data show for the first time a novel role for Nrf2 in skin physiology in response to low environmental temperature, with important implications in human connective tissue diseases with altered thermogenic responses.
T2  - BioFactors
T1  - Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation
DO  - 10.1002/biof.1931
ER  - 
@article{
author = "Zakić, Tamara and Stojanović, Sara and Janković, Aleksandra and Korać, Aleksandra and Peković‐Vaughan, Vanja and Korać, Bato",
year = "2022",
abstract = "Adaptive responses to environmental and physiological challenges, including exposure to low environmental temperature, require extensive structural, redox, and metabolic reprogramming. Detailed molecular mechanisms of such processes in the skin are lacking, especially the role of nuclear factor erythroid 2-related factor 2 (Nrf2) and other closely related redox-sensitive transcription factors Nrf1, Nrf3, and nuclear respiratory factor (NRF1). To investigate the role of Nrf2, we examined redox and metabolic responses in the skin of wild-type (WT) mice and mice lacking functional Nrf2 (Nrf2 KO) at room (RT, 24 ± 1°C) and cold (4 ± 1°C) temperature. Our results demonstrate distinct expression profiles of major enzymes involved in antioxidant defense and key metabolic and mitochondrial pathways in the skin, depending on the functional Nrf2 and/or cold stimulus. Nrf2 KO mice at RT displayed profound alterations in redox, mitochondrial and metabolic responses, generally akin to cold-induced skin responses in WT mice. Immunohistochemical analyses of skin cell compartments (keratinocytes, fibroblasts, hair follicle, and sebaceous gland) and spatial locations (nucleus and cytoplasm) revealed synergistic interactions between members of the Nrf transcription factor family as part of redox-metabolic reprogramming in WT mice upon cold acclimation. In contrast, Nrf2 KO mice at RT showed loss of NRF1 expression and a compensatory activation of Nrf1/Nrf3, which was abolished upon cold, concomitant with blunted redox-metabolic responses. These data show for the first time a novel role for Nrf2 in skin physiology in response to low environmental temperature, with important implications in human connective tissue diseases with altered thermogenic responses.",
journal = "BioFactors",
title = "Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation",
doi = "10.1002/biof.1931"
}
Zakić, T., Stojanović, S., Janković, A., Korać, A., Peković‐Vaughan, V.,& Korać, B.. (2022). Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation. in BioFactors.
https://doi.org/10.1002/biof.1931
Zakić T, Stojanović S, Janković A, Korać A, Peković‐Vaughan V, Korać B. Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation. in BioFactors. 2022;.
doi:10.1002/biof.1931 .
Zakić, Tamara, Stojanović, Sara, Janković, Aleksandra, Korać, Aleksandra, Peković‐Vaughan, Vanja, Korać, Bato, "Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation" in BioFactors (2022),
https://doi.org/10.1002/biof.1931 . .

Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue

Kalezić, Anđelika; Udički, Mirjana; Srdić Galić, Biljana; Korać, Aleksandra; Janković, Aleksandra; Korać, Bato

(Society for Free Radical Research-Europe, 2022)

TY  - CONF
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5126
AB  - 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.
PB  - Society for Free Radical Research-Europe
C3  - Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
T1  - Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue
DO  - 10.1016/j.freeradbiomed.2022.06.154
ER  - 
@conference{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2022",
abstract = "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.",
publisher = "Society for Free Radical Research-Europe",
journal = "Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium",
title = "Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue",
doi = "10.1016/j.freeradbiomed.2022.06.154"
}
Kalezić, A., Udički, M., Srdić Galić, B., Korać, A., Janković, A.,& Korać, B.. (2022). Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
Society for Free Radical Research-Europe..
https://doi.org/10.1016/j.freeradbiomed.2022.06.154
Kalezić A, Udički M, Srdić Galić B, Korać A, Janković A, Korać B. Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium. 2022;.
doi:10.1016/j.freeradbiomed.2022.06.154 .
Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue" in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium (2022),
https://doi.org/10.1016/j.freeradbiomed.2022.06.154 . .