Association between serum leptin levels and breast cancer risk

Hui, Pei; Deng, Lan; Cui, Jiaqi; Shi, Lin; Yang, Yichun; Luo, Jiang-Hui; Qin, Dan; Wang, Li

doi:10.1097/md.0000000000011345

Cited by 84 publications

(68 citation statements)

References 47 publications

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“…In addition, this adipokine is able to reduce the effectiveness of antineoplastic molecules such as 5-fluorouracil, taxol, or vinblastine, as well as antiestrogens such as Tx [23]. Clinical studies confirmed a positive association between serum leptin levels and breast cancer risk particularly in overweight/obese women [24]. However, our results did not show the involvement of leptin in the resistance of hormonal therapies in our model.…”

Section: Discussioncontrasting

confidence: 54%

Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin

et al. 2019

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Obesity, a recognized risk factor for breast cancer in postmenopausal women, is associated with higher mortality rates regardless of menopausal status, which could in part be explained by therapeutic escape. Indeed, adipose microenvironment has been described to influence the efficiency of chemo- and hormonal therapies. Residual cancer stem cells could also have a key role in this process. To understand the mechanisms involved in the reduced efficacy of hormonal therapy on breast cancer cells in the presence of adipose secretome, human adipose stem cells (hMAD cell line) differentiated into mature adipocytes were co-cultured with mammary breast cancer cells and treated with hormonal therapies (tamoxifen, fulvestrant). Proliferation and apoptosis were measured (fluorescence test, impedancemetry, cytometry) and the gene expression profile was evaluated. Cancer stem cells were isolated from mammospheres made from MCF-7. The impact of chemo- and hormonal therapies and leptin was evaluated in this population. hMAD-differentiated mature adipocytes and their secretions were able to increase mammary cancer cell proliferation and to suppress the antiproliferative effect of tamoxifen, confirming previous data and validating our model. Apoptosis and cell cycle did not seem to be involved in this process. The evaluation of gene expression profiles suggested that STAT3 could be a possible target. On the contrary, leptin did not seem to be involved. The study of isolated cancer stem cells revealed that their proliferation was stimulated in the presence of anticancer therapies (tamoxifen, fulvestrant, doxorubicine) and leptin. Our study confirmed the role of adipocytes and their secretome, but above all, the role of communication between adipose and cancer cells in interfering with the efficiency of hormonal therapy. Among the pathophysiological mechanisms involved, leptin does not seem to interfere with the estrogenic pathway but seems to promote the proliferation of cancer stem cells.

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Section: Discussioncontrasting

confidence: 54%

Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin

et al. 2019

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“…Current data regarding to the association between serum leptin levels and MT development are controversial. Some studies suggested high levels of serum leptin as a biomarker for breast cancer development [27,28]. Since we determined no significant difference in serum leptin levels between MT-positive and MT-negative mice, our results are in accordance with the previous studies reporting no correlation between serum leptin levels and breast cancer development [14,16,25].…”

Section: Discussionsupporting

confidence: 92%

Leptin Signaling in Liver Tissue of a Transgenic Breast Cancer Mouse Model

Tuna¹,

Cleary²,

Demirel³

et al. 2020

Cureus

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Leptin, an adipocytokine, is secreted from various tissues including the liver. The roles of both leptin and leptin receptor (ObR) in numerous pathophysiological conditions including mammary tumor (MT) development have been reported. However, the roles of leptin signalingrelated proteins in the liver have not been reported previously in MT development. The objective of this study was to examine the expression levels of leptin and ObR in liver tissue of a transgenic breast cancer mouse model to investigate whether the roles of leptin in MT development are systemic or local. MMTV-TGF-α transgenic female mice were fed ad-libitum from week 10 up to week 74. Protein expression levels of leptin and ObR were measured in liver tissues of 74-week-old MMTV-TGF-α mice with and without MT by western blot. Serum leptin and insulin levels were measured using a enzyme-linked immunosorbent assay. Protein expression levels of leptin and ObR were similar in mice with MT compared to the ones without MT. Serum leptin and insulin levels were also not significantly different between the two groups. These results indicate that the effects of leptin signaling in MT development might be important at a local tissue level, such as mammary fat pad, and not as important at a systemic level.

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“…Mice with adipose MCP1 deficiency exhibited lower plasma concentrations of PAI1, leptin, and resistin, particularly those fed the HFD. PAI1 (34,35), leptin (36,37), and resistin (38,39) are proinflammatory cytokines with demonstrated cancer-promoting potential. Depletion of PAI1 inhibited spontaneous metastasis of LLC (33), knockout of leptin receptors mitigated mammary tumorigenesis mediated by mouse mammary tumor virus (40), and inhibition of resistin expression suppressed experimental metastasis of chondrosarcoma in mice (41).…”

Section: Discussionmentioning

confidence: 99%

Adipose-specific Monocyte Chemotactic Protein-1 Deficiency Reduces Pulmonary Metastasis of Lewis Lung Carcinoma in Mice

Sundaram

Yan

2019

Anticancer Res

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Aim: Monocyte chemotactic protein-1 (MCP1) is a potent adipokine. This study tested the hypothesis that adiposeproduced MCP1 contributes to metastasis. Materials and Methods: In a spontaneous metastasis model of Lewis lung carcinoma (LLC), male adipose MCP1-deficient (Mcp1 −/− ) and wild-type (WT) mice were fed the AIN93G diet or a high-fat diet (HFD) for 11 weeks. Lung metastasis from a subcutaneous tumor was the primary endpoint. Results: The adipose expression of MCP1 was lower in Mcp1 −/− mice than in WT controls. The HFD increased the number of lung metastases in WT mice. The number of metastasis was significantly lower in the HFD-fed Mcp1 −/− mice than in the HFD-fed WT mice. Compared to the WT mice, adipose MCP1 deficiency lowered plasma concentrations of insulin, proinflammatory adipokines (leptin, plasminogen activator inhibitor-1, and resistin), and angiogenic markers (vascular endothelial growth factor, hepatocyte growth factor, and angiopoietin-2). Conclusion: Adipose MCP1 deficiency attenuates HFD-enhanced pulmonary metastasis of LLC.

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Association between serum leptin levels and breast cancer risk

Cited by 84 publications

References 47 publications

Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin

Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin

Leptin Signaling in Liver Tissue of a Transgenic Breast Cancer Mouse Model

Adipose-specific Monocyte Chemotactic Protein-1 Deficiency Reduces Pulmonary Metastasis of Lewis Lung Carcinoma in Mice

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