Slc7a8 Deletion Is Protective against Diet-Induced Obesity and Attenuates Lipid Accumulation in Multiple Organs

Pitere, Reabetswe R.; Heerden, Marlene B. van; Pepper, Michael Sean; Ambele, Melvin Anyasi

doi:10.3390/biology11020311

Cited by 11 publications

(9 citation statements)

References 42 publications

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“…Hematoxylin and eosin (H&E) staining was performed as previously described, 42 , 43 and immunohistochemical analysis for CD163 and CD3 staining was conducted with minor modifications as previously described. 42 , 43 Formalin‐fixed paraffin‐embedded (FFPE) tissue blocks were cut into 3‐micron sections and baked overnight at 58°C. After deparaffinizing the slides in xylene, they were hydrated with decreasing concentrations of alcohol to distilled water.…”

Section: Methodsmentioning

confidence: 99%

“…Lung and mammary tissues were collected from both euthanized 2-ME treated and control group mice and fixed in 10% neutral buffered formalin. Hematoxylin and eosin (H&E) staining was performed as previously described, 42,43 and immunohistochemical analysis for CD163 and CD3 staining was conducted with minor modifications as previously described. 42,43 Formalin-fixed paraffin-embedded (FFPE) tissue blocks were cut into 3-micron sections and baked overnight at was used for analysis.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

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Effect of 2‐methoxyestradiol on mammary tumor initiation and progression

Peta,

Durandt,

van Heerden

et al. 2024

Cancer Reports

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BackgroundThe anti‐cancer agent 2‐methoxyestradiol (2‐ME) has been shown to have anti‐proliferative and anti‐angiogenic properties. Previously, the effect of 2‐ME on early‐ and late‐stage breast cancer (BC) was investigated in vivo using a transgenic mouse model (FVB/N‐Tg(MMTV‐PyVT)) of spontaneous mammary carcinoma. Anti‐tumor effects were observed in late‐stage BC with no effect on early‐stage BC. Given the contrasting results obtained from the different BC stages, we have now investigated the effect of 2‐ME when administered before the appearance of palpable tumors.MethodsEach mouse received 100 mg/kg 2‐ME on day 30 after birth, twice per week for 28 days, while control mice received vehicle only. Animals were terminated on day 59. Lung and mammary tissue were obtained for immunohistochemical analysis of CD163 and CD3 expression, and histological examination was performed to analyze tumor necrosis. Additionally, blood samples were collected to measure plasma cytokine levels.Results2‐ME increased tumor mass when compared to the untreated animals (p = .0139). The pro‐tumorigenic activity of 2‐ME was accompanied by lower CD3+ T‐cell numbers in the tumor microenvironment (TME) and high levels of the pro‐inflammatory cytokine interleukin (IL)‐1β. Conversely, 2‐ME‐treatment resulted in fewer CD163+ cells detectable in the TME, increased levels of tumor necrosis, increased IL‐10 plasma levels, and low IL‐6 and IL‐27 plasma levels.ConclusionTaken together, these findings suggest that 2‐ME promotes early‐stage BC development.

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Section: Methodsmentioning

confidence: 99%

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Effect of 2‐methoxyestradiol on mammary tumor initiation and progression

Peta,

Durandt,

van Heerden

et al. 2024

Cancer Reports

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“…Lung and mammary tissues were collected from killed 2‐ME‐treated and control group mice, and were fixed in 10% neutral buffered formalin. Haematoxylin and eosin (H&E) staining was performed as previously described 38,39 . IHC analysis for CD163 and CD3 was also performed according to previously described protocols 38,39 with slight modifications.…”

Section: Methodsmentioning

confidence: 99%

Effect of 2‐methoxyestradiol treatment on early‐ and late‐stage breast cancer progression in a mouse model

Peta,

Durandt,

van Heerden

et al. 2023

Cell Biochemistry & Function

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The prevalence of breast cancer (BC) continues to increase and is the leading cause of cancer deaths in many countries. Numerous in vitro and in vivo studies have demonstrated that 2‐methoxyestradiol (2‐ME) has antiproliferative and antiangiogenic effects in BC, thereby inhibiting tumour growth and metastasis. We compared the effect of 2‐ME in early‐ and late‐stage BC using a transgenic mouse model—FVB/N‐Tg(MMTV‐PyVT)—of spontaneously development of aggressive mammary carcinoma with lung metastasis. Mice received 100 mg/kg 2‐ME treatment immediately when palpable mammary tumours were identified (early‐stage BC; Experimental group 1) and 28 days after palpable mammary tumours were detected (late‐stage BC; Experimental group 2). 2‐ME was administered via oral gavage three times a week for 28 days after initiation of treatment, whereas control mice received the vehicle containing 10% dimethyl sulfoxide and 90% sunflower oil for the same duration as the treatment group. Mammary tumours were measured weekly over the 28 days and at termination, blood, mammary and lung tissue were collected for analysis. Mice with a tumour volume threshold of 4000 mm3 were killed before the treatment regime was completed. 2‐ME treatment of early‐stage BC led to lower levels of mammary tumour necrosis, whereas tumour mass and volume were increased. Additionally, necrotic lesions and anti‐inflammatory CD163‐expressing cells were more frequent in pulmonary metastatic tumours in this group. In contrast, 2‐ME treatment of late‐stage BC inhibited tumour growth over the 28‐day period and resulted in increased CD3+ cell number and tumour necrosis. Furthermore, 2‐ME treatment slowed down pulmonary metastasis but did not increase survival of late‐stage BC mice. Besides late‐stage tumour necrosis, none of the other results were statistically significant. This study demonstrates that 2‐ME treatment has an antitumour effect on late‐stage BC, however, with no increase in survival rate, whereas the treatment failed to demonstrate any benefit in early‐stage BC.

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“…Lung and mammary tissues were collected from euthanized 2-ME treated and control group mice and xed in 10% neutral buffered formalin. Haematoxylin and eosin (H&E) staining was performed as previously described [38,39]. Immunohistochemical analysis for CD163 and CD3 was also performed according to previously described protocols [38,39] with slight modi cations.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

“…Haematoxylin and eosin (H&E) staining was performed as previously described [38,39]. Immunohistochemical analysis for CD163 and CD3 was also performed according to previously described protocols [38,39] with slight modi cations. Brie y, formalin-xed para n-embedded (FFPE) tissue blocks were cut into 3-micron sections and baked in a 58°C oven overnight.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Effect of 2-methoxyestradiol treatment on early- and late-stage breast cancer progression in a mouse model

Peta

Durandt

Heerden

et al. 2023

Preprint

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BACKGROUND: The prevalence of breast cancer (BC) continues to increase and is the leading cause of cancer deaths in many countries. Numerous in vitro and in vivo studies have demonstrated that 2-methoxyestradiol (2-ME) has antiproliferative and antiangiogenic effects in BC thereby inhibiting tumour growth and metastasis. We compared the effect of 2-ME in early and late-stage BC using a transgenic mouse model – FVB/N-Tg(MMTV-PyVT) – of spontaneously development of aggressive mammary carcinoma with lung metastasis. METHODS: Mice received 100 mg/kg 2-ME treatment immediately when palpable mammary tumours were identified (early-stage BC; experimental group 1) and 28 days after palpable mammary tumours were detected (late-stage BC; experimental group 2). 2-ME was administered via oral gavage three times a week for 28 days after initiation of treatment, while control mice received the vehicle containing 10% dimethyl sulfoxide (DMSO) and 90% sunflower oil for the same duration as the treatment group. Mammary tumours were measured weekly over the 28-day period and at termination, blood, mammary and lung tissue were collected for analysis. Mice with a tumour volume threshold of 4000mm3 were euthanized before the treatment regime was completed. RESULTS: 2-ME treatment of early-stage BC led to lower levels of mammary tumour necrosis, while tumour mass and volume were increased. Additionally, necrotic lesions and anti-inflammatory CD163 expressing cells were more frequent in pulmonary metastatic tumours in this group. In contrast, 2-ME treatment of late-stage BC inhibited tumour growth over the 28-day period, and resulted in increased CD3+ cell number and tumour necrosis. Furthermore, 2-ME treatment slowed down pulmonary metastasis, but did not increase survival of late-stage BC mice. Besides late-stage tumour necrosis, none of the other results were statistically significant. CONCLUSION: This study demonstrates that 2-ME treatment has an antitumour effect on late-stage BC, however with no increase in survival rate, while the treatment failed to demonstrate any benefit in early-stage BC.

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Slc7a8 Deletion Is Protective against Diet-Induced Obesity and Attenuates Lipid Accumulation in Multiple Organs

Cited by 11 publications

References 42 publications

Effect of 2‐methoxyestradiol on mammary tumor initiation and progression

Effect of 2‐methoxyestradiol on mammary tumor initiation and progression

Effect of 2‐methoxyestradiol treatment on early‐ and late‐stage breast cancer progression in a mouse model

Effect of 2-methoxyestradiol treatment on early- and late-stage breast cancer progression in a mouse model

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