Udički, Mirjana

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  • Udički, Mirjana (4)
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Author's Bibliography

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 . .

Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.

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

(Elsevier BV, 2021)

TY  - JOUR
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Aleksić, Marija
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33765617
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4175
AB  - One of the underlying mechanisms that could link breast cancer and obesity is shifted redox homeostasis in the tumor microenvironment. To reveal the relationship between the malignant phenotype and obesity, we compared redox profiles of breast tumor and tumor-associated adipose tissue from premenopausal women: normal-weight with benign tumors, overweight/obese with benign tumors, normal-weight with malignant tumors, and overweight/obese with malignant tumors. Namely, we examined the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression and activity of main antioxidant defense (AD) enzymes: copper, zinc- and manganese superoxide dismutase, catalase, and glutathione peroxidase, as well as the level of 4-hydroxy-2-nonenal (4-HNE) modified proteins. Higher protein expression and activity of AD enzymes were found in malignant tumor tissue than benign tumor tissue, irrespective of obesity. Nevertheless, malignant tumor tissue of overweight/obese women was characterized by higher protein expression of Nrf2 and weaker immunopositivity for 4-HNE modified proteins. In malignant tumor-associated adipose tissue, the redox profile was clearly related to obesity. Higher Nrf2 protein expression and higher AD enzyme levels were observed in normal-weight women, while stronger immunopositivity for 4-HNE modified proteins was found in overweight/obese women. The results suggest that the complex interplay between obesity and malignancy involves redox-sensitive pathways in breast tumor and tumor-associated adipose tissue.
PB  - Elsevier BV
T2  - Redox Biology
T1  - Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.
VL  - 41
DO  - 10.1016/j.redox.2021.101939
SP  - 101939
ER  - 
@article{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Aleksić, Marija and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "One of the underlying mechanisms that could link breast cancer and obesity is shifted redox homeostasis in the tumor microenvironment. To reveal the relationship between the malignant phenotype and obesity, we compared redox profiles of breast tumor and tumor-associated adipose tissue from premenopausal women: normal-weight with benign tumors, overweight/obese with benign tumors, normal-weight with malignant tumors, and overweight/obese with malignant tumors. Namely, we examined the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression and activity of main antioxidant defense (AD) enzymes: copper, zinc- and manganese superoxide dismutase, catalase, and glutathione peroxidase, as well as the level of 4-hydroxy-2-nonenal (4-HNE) modified proteins. Higher protein expression and activity of AD enzymes were found in malignant tumor tissue than benign tumor tissue, irrespective of obesity. Nevertheless, malignant tumor tissue of overweight/obese women was characterized by higher protein expression of Nrf2 and weaker immunopositivity for 4-HNE modified proteins. In malignant tumor-associated adipose tissue, the redox profile was clearly related to obesity. Higher Nrf2 protein expression and higher AD enzyme levels were observed in normal-weight women, while stronger immunopositivity for 4-HNE modified proteins was found in overweight/obese women. The results suggest that the complex interplay between obesity and malignancy involves redox-sensitive pathways in breast tumor and tumor-associated adipose tissue.",
publisher = "Elsevier BV",
journal = "Redox Biology",
title = "Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.",
volume = "41",
doi = "10.1016/j.redox.2021.101939",
pages = "101939"
}
Kalezić, A., Udički, M., Srdić Galić, B., Aleksić, M., Korać, A., Janković, A.,& Korać, B.. (2021). Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.. in Redox Biology
Elsevier BV., 41, 101939.
https://doi.org/10.1016/j.redox.2021.101939
Kalezić A, Udički M, Srdić Galić B, Aleksić M, Korać A, Janković A, Korać B. Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.. in Redox Biology. 2021;41:101939.
doi:10.1016/j.redox.2021.101939 .
Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Aleksić, Marija, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy." in Redox Biology, 41 (2021):101939,
https://doi.org/10.1016/j.redox.2021.101939 . .
3
6
2
5

Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis

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

(2021)

TY  - JOUR
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Aleksić, Marija
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - https://www.mdpi.com/2072-6694/13/11/2731
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4407
AB  - Typical features of the breast malignant phenotype rely on metabolic reprogramming of cancer cells and their interaction with surrounding adipocytes. Obesity is strongly associated with breast cancer mortality, yet the effects of obesity on metabolic reprogramming of cancer and cancer-associated adipose tissue remain largely unknown. Paired biopsies of breast tumor tissue and adipose tissue from premenopausal women were divided according to pathohistological analyses and body mass index on normal-weight and overweight/obese with benign or malignant tumors. We investigated the protein expression of key regulatory enzymes of glycolysis, pentose phosphate pathway (PPP), and glycogen synthesis. Breast cancer tissue showed a simultaneous increase in 5′-AMP-activated protein kinase (AMPK) protein expression with typical features of the Warburg effect, including hexokinase 2 (HK 2) overexpression and its association with mitochondrial voltage-dependent anion-selective channel protein 1, associated with an overexpression of rate-limiting enzymes of glycolysis (phosphofructokinase 1—PFK-1) and pentose phosphate pathway (glucose-6-phosphate dehydrogenase—G6PDH). In parallel, cancer-associated adipose tissue showed increased AMPK protein expression with overexpression of HK 2 and G6PDH in line with increased PPP activity. Moreover, important obesity-associated differences in glucose metabolism were observed in breast cancer tissue showing prominent glycogen deposition and higher glycogen synthase kinase-3 protein expression in normal-weight women and higher PFK-1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein expression in overweight/obese women. In conclusion, metabolic reprogramming of glycolysis contributes to tissue-specific Warburg effect in breast cancer and cancer-associated adipose tissue.
T2  - Cancers
T1  - Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis
IS  - 11
VL  - 13
DO  - 10.3390/cancers13112731
SP  - 2731
ER  - 
@article{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Aleksić, Marija and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "Typical features of the breast malignant phenotype rely on metabolic reprogramming of cancer cells and their interaction with surrounding adipocytes. Obesity is strongly associated with breast cancer mortality, yet the effects of obesity on metabolic reprogramming of cancer and cancer-associated adipose tissue remain largely unknown. Paired biopsies of breast tumor tissue and adipose tissue from premenopausal women were divided according to pathohistological analyses and body mass index on normal-weight and overweight/obese with benign or malignant tumors. We investigated the protein expression of key regulatory enzymes of glycolysis, pentose phosphate pathway (PPP), and glycogen synthesis. Breast cancer tissue showed a simultaneous increase in 5′-AMP-activated protein kinase (AMPK) protein expression with typical features of the Warburg effect, including hexokinase 2 (HK 2) overexpression and its association with mitochondrial voltage-dependent anion-selective channel protein 1, associated with an overexpression of rate-limiting enzymes of glycolysis (phosphofructokinase 1—PFK-1) and pentose phosphate pathway (glucose-6-phosphate dehydrogenase—G6PDH). In parallel, cancer-associated adipose tissue showed increased AMPK protein expression with overexpression of HK 2 and G6PDH in line with increased PPP activity. Moreover, important obesity-associated differences in glucose metabolism were observed in breast cancer tissue showing prominent glycogen deposition and higher glycogen synthase kinase-3 protein expression in normal-weight women and higher PFK-1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein expression in overweight/obese women. In conclusion, metabolic reprogramming of glycolysis contributes to tissue-specific Warburg effect in breast cancer and cancer-associated adipose tissue.",
journal = "Cancers",
title = "Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis",
number = "11",
volume = "13",
doi = "10.3390/cancers13112731",
pages = "2731"
}
Kalezić, A., Udički, M., Srdić Galić, B., Aleksić, M., Korać, A., Janković, A.,& Korać, B.. (2021). Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis. in Cancers, 13(11), 2731.
https://doi.org/10.3390/cancers13112731
Kalezić A, Udički M, Srdić Galić B, Aleksić M, Korać A, Janković A, Korać B. Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis. in Cancers. 2021;13(11):2731.
doi:10.3390/cancers13112731 .
Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Aleksić, Marija, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis" in Cancers, 13, no. 11 (2021):2731,
https://doi.org/10.3390/cancers13112731 . .
21
2
19

AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer

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

(Elsevier BV, 2021)

TY  - CONF
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4859
AB  - Breast cancer behaves as a complex pseudo-organ where the adaptive behavior of cancer cells is deeply context-dependent, reflecting various local and systemic influences. Recently, cancer-associated adipocytes emerged as critical players in cancer progression, adapting to metabolic demands of proliferating cancer cells and responding through the supply of diverse energy substrates. To decipher underlying mechanisms that enable such plastic response, we cross-examined biopsies of cancer-associated adipose tissue from normal-weight and overweight women with invasive ductal carcinoma compared to mammary adipose tissue of weight-matched women with benign fibroadenoma. To that end, we analyzed mitochondrial copy number and master regulators of energy and redox homeostasis (AMP-activated protein kinase – AMPK and nuclear factor erythroid 2-related factor 2 – Nrf2), followed by key enzymes in their downstream pathways such as glycolysis, pentose phosphate pathway, fatty acid oxidation, and antioxidant defense. Compared to mammary adipose tissue, cancer-associated adipose tissue showed concomitantly higher AMPK and Nrf2 protein expression followed by overexpression of hexokinase 2, glucose-6-phosphate dehydrogenase, peroxisomal acyl-coenzyme A oxidase 1, first-line antioxidant defense enzymes (CuZn- and Mn- superoxide dismutase and catalase), as well as higher mitochondrial copy number. In contrast, in cancer-associated adipose tissue of obese women, a sole increase in AMPK protein expression without Nrf2 was followed by increased protein expression of analyzed metabolic enzymes but not antioxidant defense enzymes or mitochondrial copy number. The results indicate that simultaneous activation of AMPK and Nrf2 signaling promotes a specific metabolic phenotype of cancer-associated adipose tissue, resembling the Warburg effect with high mitochondrial content and increased redox homeostasis threshold. Moreover, context-dependent disruption of the AMPK–Nrf2 axis could prevent the establishment of such phenotype in obesity
PB  - Elsevier BV
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer
VL  - 177
DO  - 10.1016/j.freeradbiomed.2021.08.086
SP  - S76
EP  - S77
ER  - 
@conference{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "Breast cancer behaves as a complex pseudo-organ where the adaptive behavior of cancer cells is deeply context-dependent, reflecting various local and systemic influences. Recently, cancer-associated adipocytes emerged as critical players in cancer progression, adapting to metabolic demands of proliferating cancer cells and responding through the supply of diverse energy substrates. To decipher underlying mechanisms that enable such plastic response, we cross-examined biopsies of cancer-associated adipose tissue from normal-weight and overweight women with invasive ductal carcinoma compared to mammary adipose tissue of weight-matched women with benign fibroadenoma. To that end, we analyzed mitochondrial copy number and master regulators of energy and redox homeostasis (AMP-activated protein kinase – AMPK and nuclear factor erythroid 2-related factor 2 – Nrf2), followed by key enzymes in their downstream pathways such as glycolysis, pentose phosphate pathway, fatty acid oxidation, and antioxidant defense. Compared to mammary adipose tissue, cancer-associated adipose tissue showed concomitantly higher AMPK and Nrf2 protein expression followed by overexpression of hexokinase 2, glucose-6-phosphate dehydrogenase, peroxisomal acyl-coenzyme A oxidase 1, first-line antioxidant defense enzymes (CuZn- and Mn- superoxide dismutase and catalase), as well as higher mitochondrial copy number. In contrast, in cancer-associated adipose tissue of obese women, a sole increase in AMPK protein expression without Nrf2 was followed by increased protein expression of analyzed metabolic enzymes but not antioxidant defense enzymes or mitochondrial copy number. The results indicate that simultaneous activation of AMPK and Nrf2 signaling promotes a specific metabolic phenotype of cancer-associated adipose tissue, resembling the Warburg effect with high mitochondrial content and increased redox homeostasis threshold. Moreover, context-dependent disruption of the AMPK–Nrf2 axis could prevent the establishment of such phenotype in obesity",
publisher = "Elsevier BV, Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer",
volume = "177",
doi = "10.1016/j.freeradbiomed.2021.08.086",
pages = "S76-S77"
}
Kalezić, A., Udički, M., Srdić Galić, B., Korać, A., Janković, A.,& Korać, B.. (2021). AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier BV., 177, S76-S77.
https://doi.org/10.1016/j.freeradbiomed.2021.08.086
Kalezić A, Udički M, Srdić Galić B, Korać A, Janković A, Korać B. AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;177:S76-S77.
doi:10.1016/j.freeradbiomed.2021.08.086 .
Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia, 177 (2021):S76-S77,
https://doi.org/10.1016/j.freeradbiomed.2021.08.086 . .