The Role of Adipokines in Breast Cancer: Current Evidence and Perspectives

Christodoulatos, Gerasimos Socrates; Spyrou, Nikolaos; Kadillari, Jona; Psallida, Sotiria; Dalamaga, Maria

doi:10.1007/s13679-019-00364-y

Cited by 69 publications

(62 citation statements)

References 219 publications

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“…The mammary gland involution is described by the gradual replacement of breast epithelium and stroma by collagen and adipose tissue and by the regression of type 2-3 lobules to type 1 lobules [52]. Many studies focus on obesity-related unbalance resulting in the disturbed secretion of inflammatory molecules named adipokines by the adipose tissue [53][54][55][56][57][58]. Interestingly, adipogenesis also occurs during breast involution, so that adipokines overexpression could appear during this specific step.…”

Section: Adipogenesismentioning

confidence: 99%

Role of Secreted Frizzled-Related Protein 1 in Early Mammary Gland Tumorigenesis and Its Regulation in Breast Microenvironment

Clemenceau

Diorio

Durocher

2020

Cells

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In mice, the lack of secreted frizzled-related protein 1 (SFRP1) is responsible for mammogenesis and hyperplasia, while, in bovines, its overexpression is associated with post-lactational mammary gland involution. Interestingly, there are no reports dealing with the role of SFRP1 in female involution. However, SFRP1 dysregulation is largely associated with human tumorigenesis in the literature. Indeed, the lack of SFRP1 is associated with both tumor development and patient prognosis. Considering the increased risk of breast tumor development associated with incomplete mammary gland involution, it is crucial to demystify the “grey zone” between physiological age-related involution and tumorigenesis. In this review, we explore the functions of SFRP1 involved in the breast involution processes to understand the perturbations driven by the disappearance of SFRP1 in mammary tissue. Moreover, we question the presence of recurrent microcalcifications identified by mammography. In bone metastases from prostate primary tumor, overexpression of SFRP1 results in an osteolytic response of the tumor cells. Hence, we explore the hypothesis of an osteoblastic differentiation of mammary cells induced by the lack of SFRP1 during lobular involution, resulting in a new accumulation of hydroxyapatite crystals in the breast tissue.

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Section: Adipogenesismentioning

confidence: 99%

Role of Secreted Frizzled-Related Protein 1 in Early Mammary Gland Tumorigenesis and Its Regulation in Breast Microenvironment

Clemenceau

Diorio

Durocher

2020

Cells

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“…The adipokine resistin participates in several physiologic and pathologic processes throughout the body, including metabolism, inflammation, autoimmunity, and various cancers, including CRC [3][4][5][6][7][8][9]. Previous research has documented an association between higher levels of circulating resistin and an increased risk for CRC [10].…”

Section: Discussionmentioning

confidence: 99%

“…Resistin is a cytokine secreted by adipocytes that participates in the body's metabolism, inflammation, and autoimmunity through multiple molecular pathways [3]. While initial research focused on obesity and insulin resistance, resistin was later implicated in the occurrence and progression of various malignant tumors [4][5][6][7][8][9]. Evidence demonstrates that higher levels of circulating resistin increase the risk of developing CRC [10].…”

Section: Introductionmentioning

confidence: 99%

High Expression of Both Resistin and Fascin-1 Predicts a Poor Prognosis in Patients with Colorectal Cancer

Wang

Huang

et al. 2020

BioMed Research International

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Emerging evidence indicates that resistin and fascin-1 may possess a causal role in the development of several types of cancers. However, the clinical significance of resistin expression in colorectal cancer (CRC) tissues is unclear, and there are no reports of any correlation between resistin and fascin-1. Our analyses explored the expression of resistin in CRC tissue and analyzed the clinical and prognostic significance of the observed positive correlation between resistin and fascin-1. The rate of strongly positive resistin expression (27.5%) was significantly higher in CRC tissues than in normal colorectal tissues (5.2%). Strongly positive resistin expression is related to multiple poor prognostic factors in CRC, including depth of tumor invasion, lymph node metastasis, and tumor stage. In this study, survival was worse in CRC patients with high levels of both resistin and fascin-1 expression than in those with high levels of only one protein or normal levels of both proteins. We suggest that a combined high level of resistin and fascin-1 expression correlates reliably with survival in CRC, so it may serve as a potential therapeutic target.

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“…This configuration of circulating adipokines is widely accepted in the literature, since body composition changes with age, especially the amount of body fat, which leads to the attenuation of energy homeostasis and variation in adipose tissue metabolism [ 2 , 3 , 11 , 21 , 22 ]. Leptin and adiponectin in cancer biology work in an inverse manner, since leptin plays a crucial role in the promotion of tumour angiogenesis, cell invasion, and metastasis, whereas adiponectin possesses anti-tumour properties, including anti-proliferative, anti-migratory, and pro-apoptotic actions [ 2 , 3 , 21 ]. Our findings are in line with previous studies, which demonstrated that leptin positively correlates with breast cancer risk, while a low adiponectin concentration is linked to a higher risk of breast cancer [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Pre-Operative Combination of Normal BMI with Elevated YKL-40 and Leptin but Lower Adiponectin Level Is Linked to a Higher Risk of Breast Cancer Relapse: A Report of Four-Year Follow-Up Study

Bielawski

Rhone²,

Bulsa

et al. 2020

JCM

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Adipokines are powerful agents involved in the development of obesity-dependent cancers. This prospective study aimed to investigate the association between pre-treatment body mass index (BMI) and serum YKL-40, leptin, and adiponectin concentrations as well as the plasma activity of tissue factor (TF) and the future prognosis of early, non-metastatic breast cancer (BrC) subjects. The serum levels of YKL-40, leptin, and adiponectin as well as plasma TF activity, anthropometric parameters, and clinicopathological parameters were analysed in 81 treatment-naïve females with invasive BrC. The predictive value of YKL-40, BMI, leptin, adiponectin, and TF was determined with a 95% confidence interval (CI). Kaplan–Meier plots and log-rank and F Cox tests were used to determine the clinical outcomes of progression-free survival (PFS). The median follow-up duration was 44 months with complete follow-up for the first event. Follow-up revealed a significantly higher incidence of disease relapse in BrC patients with a high baseline concentration of YKL-40 (22.22%) and TF activity (21.43%). Body mass index was an independent predictor of survival, with women who were overweight/obese being less prone to relapse (hazard ratio (HR): 0.75; 95% CI: 0.59 to 0.95). The recurrence rates for normal-weight BrC cases was 21.05% versus 7.14% for their overweight counterparts. The receiver operating characteristic analysis showed the strong ability of the analysed biomarkers to predict disease progression, with an area under the receiver operating characteristics (ROC) curve of 0.84 (95% CI, 0.823 to 0.931). In a prospective cohort of invasive BrC patients, overweight/obesity was associated with improved future outcomes. The combination of a normal BMI with high leptin and low adiponectin levels and high TF activity was associated with an increased risk of recurrence and decreased survival.

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The Role of Adipokines in Breast Cancer: Current Evidence and Perspectives

Cited by 69 publications

References 219 publications

Role of Secreted Frizzled-Related Protein 1 in Early Mammary Gland Tumorigenesis and Its Regulation in Breast Microenvironment

Role of Secreted Frizzled-Related Protein 1 in Early Mammary Gland Tumorigenesis and Its Regulation in Breast Microenvironment

High Expression of Both Resistin and Fascin-1 Predicts a Poor Prognosis in Patients with Colorectal Cancer

Pre-Operative Combination of Normal BMI with Elevated YKL-40 and Leptin but Lower Adiponectin Level Is Linked to a Higher Risk of Breast Cancer Relapse: A Report of Four-Year Follow-Up Study

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