Abstract
The mammary gland is a heterogeneous organ comprising of immune cells, surrounding adipose stromal cells, vascular cells, mammary epithelial, and cancer stem cells. In response to nutritional stimuli, dynamic interactions amongst these cell populations can be modulated, consequently leading to an alteration of the glandular function, physiology, and ultimately disease pathogenesis. For example, obesity, a chronic over-nutritional condition, is known to disrupt homeostasis within the mammary gland and increase risk of breast cancer development. In contrast, emerging evidence has demonstrated that fasting or caloric restriction can negatively impact mammary tumorigenesis. However, how fasting induces phenotypic and functional population differences in the mammary microenvironment is not well understood. In this review, we will provide a detailed overview on the effect of nutritional conditions (i.e., overnutrition or fasting) on the mammary gland microenvironment and its impact on mammary tumor progression.
Highlights
The relationship between nutrition and cancer has been well established with obesity increasing the risk and progression of breast cancer by 20–40% in post-menopausal women (Munsell et al, 2014)
Administering IL-6 neutralizing antibody abolished the effects of cancer associated fibroblasts (CAF)-induced cell migration, possibly leading to reduced metastasis (Wang et al, 2017). These findings suggest that high-fat diet (HFD)-induced obesity can reduce adipogenic differentiation of adipose stromal cells (ASC) while augmenting ASC conversion to CAF (Hillers et al, 2018)
We provided a detailed overview on of the effect of nutritional conditions such as obesity and fasting on ASCs, CAFs, immune cells, vascular cells, mammary epithelial, and cancer stem cells, all of which play an important role in the tumor microenvironment (Figure 2)
Summary
The relationship between nutrition and cancer has been well established with obesity increasing the risk and progression of breast cancer by 20–40% in post-menopausal women (Munsell et al, 2014). Depleting MDSC in obese mice protected against dietinduced metabolic dysfunction and inflammation, which was sufficient to decrease tumor volume, liver metastasis, and improve overall survival They discovered that HFD induces MDSC′ PD-L1 expression, thereby inactivating CD8+ T cell cytotoxic activity (Clements et al, 2018) and enhancing immunosuppression. HFD feeding in breast cancer cell E0771 inoculated mice decreased anti-VEGF therapy efficacy from 50 to 28% These obese tumors experienced hypovascularity, hypoxia, and increased abundance of cancerassociated adipocytes (Incio et al, 2018). As 24-h fasting in humans has been shown to increase mRNA and protein ANGPTL4 in mammary WAT (Ruppert et al, 2020), fasting may accelerate obesity-induced tumor angiogenesis As a result, this could contribute to cancer cell survival through an ample supply of oxygen and nutrients. This could enhance our knowledge and provide a potential explanation for the delayed onset observed in mammary tumor fasting studies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
