CC chemokine ligand 2 (CCL2) stimulates aromatase gene expression in mammary adipose tissue

Martínez‐Chacón, Gabriela; Yatkin, Emrah; Polari, Lauri; Dinç, Defne Deniz; Peuhu, Emilia; Hartiala, Pauliina; Saarinen, Niina M.; Mäkelä, Sari

doi:10.1096/fj.201902485rrr

Cited by 5 publications

(3 citation statements)

References 75 publications

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“…[32] CCL2 is also a pro-inflammatory factor that can activate signaling pathways related to CYP19A1 transcription, thereby contributing to the pro-inflammatory environment and aromatase expression in obesity, leading to the deterioration of menopausal-related inflammatory conditions. [33] The results from the study of the pathogenesis of psoriasis reveal that the pharmacological inhibition of MMP-9 can reduce skin vasodilation, vascular permeability, and inflammation. [34] To date, more than 200 compounds have been isolated and identified from RA, including flavonoids, saponins, and polysaccharides.…”

Section: Discussionmentioning

confidence: 99%

Predicting the anti-inflammatory mechanism of Radix Astragali using network pharmacology and molecular docking

Ren,

Ding,

et al. 2023

Medicine

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According to current research, the primary active ingredients of Radix Astragali (RA), such as saponins, flavonoids, and polysaccharides, play an important role in anti-inflammatory effects. However, the exact molecular mechanism underlying the action was not elucidated to date. Our research attempted to determine the active components in RA and to investigate the interaction between the active components and targets involved in the anti-inflammation activity by network pharmacology and molecular docking. The active components and targets of RA were screened out by TCMSP. Thereafter, through the “anti-inflammation effect” and “inflammation” as the keywords, disease targets were obtained from the GeneCards database. The PPI network was constructed with Cytoscape 3.8.0 software to screen core targets. The GO function and KEGG analysis were enriched and analyzed through the Metascape platform, obtaining the 3-dimensional view of the core targets from the PDB database, and then, performing molecular docking in AutoDock Vina, a heatmap was constructed using the binding free energies in GraphPad Prism 8. The Discovery Studio software was used for docking analysis, and eventually, the docking results were visualized. We also explored the targets and signaling pathways of Astragaloside IV acting on anti-inflammatory effects via constructing compound-disease-target-pathway network. 18 active components and 45 targets of RA were screened out. The main anti-inflammatory active components of RA were quercetin, Astragaloside IV, kaempferol, 7-O-methylisomucronulatol, and formononetin, and the strongly interacting core proteins were TNF, IL6, IL1B, TLR4, CXCL8, CCL2, IL10, VEGFA, and MMP9. The signal pathways mainly involved include Lipid and atherosclerosis, IL-17 signaling pathway, Chagas disease, leishmaniasis, and TNF signaling pathway. Moreover, molecular docking showed that the 2 most active compounds, Astragaloside IV and kaempferol, could efficiently bind with the targets TNF, TLR4, and IL10. Astragaloside IV may play a part in anti-inflammatory effects through pathways such as HIF-1 signaling pathway, Inflammatory bowel disease and Hepatitis B ect. RA exhibits the characteristic of multicomponent and multitarget synergistic effects in exerting anti-inflammatory effects and the effective component of RA is Astragaloside IV, targeting TNF, TLR4, and IL10.

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Section: Discussionmentioning

confidence: 99%

Predicting the anti-inflammatory mechanism of Radix Astragali using network pharmacology and molecular docking

Ren,

Ding,

et al. 2023

Medicine

View full text Add to dashboard Cite

show abstract

“…Another study showed that CCL2 augments estrogen production and cancer risk by activating the aromatase promoter, pI.4, via the ERK1/2 pathway. The mammary fat pads of animals with weight gain have significantly higher amounts of IL-6, CCL2, and leptin, which are positively linked with mammary aromatase reporter activity in experiments with human primary breast adipose stem cells (ASCs) and mouse mammary adipose explants 45 . Additionally, local estrogen biosynthesis via aromatase and inflammation are linked to COX-2-dependent PGE2 production in obese breast tissue.…”

Section: Tumor Stemness and Carcinogenesis In The Obese Inflammatory ...mentioning

confidence: 99%

Understanding the mechanisms underlying obesity in remodeling the breast tumor immune microenvironment: from the perspective of inflammation

Zhang

Wang

2023

Cancer Biol Med

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Obesity is a well-known modifiable risk factor for breast cancer and is considered a poor prognostic factor in pre- and post-menopausal women. While the systemic effects of obesity have been extensively studied, less is known about the mechanisms underlying obesity-associated cancer risk and the local consequences of obesity. Thus, obesity-induced inflammation has become the focus of research interest. Biologically, the development of cancer involves a complex interaction with numerous components. As the tumor immune microenvironment changes due to obesity-triggered inflammation, an increase in infiltration occurs for proinflammatory cytokines and adipokines, as well as adipocytes, immune cells, and tumor cells in the expanded adipose tissue. Complicated cellular-molecular crosstalk networks change critical pathways, mediate metabolic and immune function reprogramming, and have a significant role in tumor metastasis, proliferation, resistance, angiogenesis, and tumorigenesis. This review summarizes recent research findings on how inflammatory mediators in the in situ tumor microenvironment regulate the occurrence and development of breast cancer in the context of obesity. We analyzed the heterogeneity and potential mechanisms of the breast cancer immune microenvironment from the perspective of inflammation to provide a reference for the clinical transformation of precision targeted cancer therapy.

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“…As important inflammatory mediators, interleukin (IL)-6, tumor necrosis factor (TNF)-a, CCL2, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) catalyzed from COX-2 participate in the induction of aromatase expression in breast adipose tissue. In obese mice and subcutaneous adipose tissue from obese women, CCL2 was increased in breast adipose tissue and enhanced the glucocorticoid-mediated CYP19A1 transcription, thus promoting the pro-inflammatory milieu and aromatase expression under obesity condition (73). Hypoxiainducible factor 1a (HIF-1a) was a dominant regulator of oxygen homeostasis and could stimulate aromatase and CREB1 expression in response to tumor-derived and obesity-associated pro-inflammatory mediator PGE2 (74).…”

Section: Sex Hormonementioning

confidence: 99%

Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer

Zhao

et al. 2021

Front. Oncol.

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Obesity is defined as a chronic disease induced by an imbalance of energy homeostasis. Obesity is a widespread health problem with increasing prevalence worldwide. Breast cancer (BC) has already been the most common cancer and one of the leading causes of cancer death in women worldwide. Nowadays, the impact of the rising prevalence of obesity has been recognized as a nonnegligible issue for BC development, outcome, and management. Adipokines, insulin and insulin-like growth factor, sex hormone and the chronic inflammation state play critical roles in the vicious crosstalk between obesity and BC. Furthermore, obesity can affect the efficacy and side effects of multiple therapies such as surgery, radiotherapy, chemotherapy, endocrine therapy, immunotherapy and weight management of BC. In this review, we focus on the current landscape of the mechanisms of obesity in fueling BC and the impact of obesity on diverse therapeutic interventions. An in-depth exploration of the underlying mechanisms linking obesity and BC will improve the efficiency of the existing treatments and even provide novel treatment strategies for BC treatment.

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CC chemokine ligand 2 (CCL2) stimulates aromatase gene expression in mammary adipose tissue

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 5 publications

References 75 publications

Predicting the anti-inflammatory mechanism of Radix Astragali using network pharmacology and molecular docking

Predicting the anti-inflammatory mechanism of Radix Astragali using network pharmacology and molecular docking

Understanding the mechanisms underlying obesity in remodeling the breast tumor immune microenvironment: from the perspective of inflammation

Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer

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