1 research outputs found
The effect of adipocyte-macrophage crosstalk in obesity-related breast cancer
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-alpha 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,
adipocytemacrophage crosstalk is important in the aforementioned issues.
Increased mTORC1 signaling in obesity ensures the strong activation of
oncogenic signaling in E2R alpha-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