The effect of adipocyte–macrophage crosstalk in obesity-related breast cancer
| Autor: | İpek Işık Gönül, Ayse Basak Engin, Atilla Engin |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adipose tissue
Estrogen receptor Breast Neoplasms Tuberous Sclerosis Complex 1 Protein Proinflammatory cytokine chemistry.chemical_compound Aromatase Endocrinology Insulin resistance Breast cancer Adipocyte Adipocytes medicine Animals Humans Obesity Molecular Biology biology business.industry Macrophages medicine.disease Receptors Estrogen chemistry biology.protein Cancer research Female Tumor necrosis factor alpha business |
| Zdroj: | Journal of Molecular Endocrinology. 62:R201-R222 |
| ISSN: | 1479-6813 0952-5041 |
| DOI: | 10.1530/jme-18-0252 |
| Popis: | Adipose tissue is the primary source of many pro-inflammatory cytokines in obesity. Macrophage numbers and pro-inflammatory gene expression are positively associated with adipocyte size. Free fatty acid and tumor necrosis factor-α involve in a vicious cycle between adipocytes and macrophages aggravating inflammatory changes. Thereby, M1 macrophages form a characteristic ‘crown-like structure (CLS)’ around necrotic adipocytes in obese adipose tissue. In obese women, CLSs of breast adipose tissue are responsible for both increase in local aromatase activity and aggressive behavior of breast cancer cells. Interlinked molecular mechanisms between adipocyte–macrophage–breast cancer cells in obesity involve seven consecutive processes: Excessive release of adipocyte- and macrophage-derived inflammatory cytokines, TSC1–TSC2 complex–mTOR crosstalk, insulin resistance, endoplasmic reticulum (ER) stress and excessive oxidative stress generation, uncoupled respiration and hypoxia, SIRT1 controversy, the increased levels of aromatase activity and estrogen production. Considering elevated risks of estrogen receptor (E2R)-positive postmenopausal breast cancer growth in obesity, adipocyte–macrophage crosstalk is important in the aforementioned issues. Increased mTORC1 signaling in obesity ensures the strong activation of oncogenic signaling in E2Rα-positive breast cancer cells. Since insulin and insulin-like growth factors have been identified as tumor promoters, hyperinsulinemia is an independent risk factor for poor prognosis in breast cancer despite peripheral insulin resistance. The unpredictable effects of adipocyte-derived leptin–estrogen–macrophage axis, and sirtuin 1 (SIRT1)–adipose-resident macrophage axis in obese postmenopausal patients with breast cancer are unresolved mechanistic gaps in the molecular links between the tumor growth and adipocytokines. |
| Databáze: | OpenAIRE |
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