Abstract
Obesity rates are climbing, representing a confounding and contributing factor to many disease states, including cancer. With respect to breast cancer, obesity plays a prominent role in the etiology of this disease, with certain subtypes such as triple-negative breast cancer having a strong correlation between obesity and poor outcomes. Therefore, it is critical to examine the obesity-related alterations to the normal stroma and the tumor microenvironment (TME). Adipocytes and adipose stem cells (ASCs) are major components of breast tissue stroma that have essential functions in both physiological and pathological states, including energy storage and metabolic homeostasis, physical support of breast epithelial cells, and directing inflammatory and wound healing responses through secreted factors. However, these processes can become dysregulated in both metabolic disorders, such as obesity and also in the context of breast cancer. Given the well-established obesity-neoplasia axis, it is critical to understand how interactions between different cell types in the tumor microenvironment, including adipocytes and ASCs, govern carcinogenesis, tumorigenesis, and ultimately metastasis. ASCs and adipocytes have multifactorial roles in cancer progression; however, due to the plastic nature of these cells, they also have a role in regenerative medicine, making them promising tools for tissue engineering. At the physiological level, the interactions between obesity and breast cancer have been examined; here, we will delineate the mechanisms that regulate ASCs and adipocytes in these different contexts through interactions between cancer cells, immune cells, and other cell types present in the tumor microenvironment. We will define the current state of understanding of how adipocytes and ASCs contribute to tumor progression through their role in the tumor microenvironment and how this is altered in the context of obesity. We will also introduce recent developments in utilizing adipocytes and ASCs in novel approaches to breast reconstruction and regenerative medicine.
Highlights
Between 1999 and 2018, the prevalence of obesity in the United States climbed from 30.5 to 42.3% (Hales et al, 2020)
In the context of obesity, increased leptin signaling between adipose stem cells (ASCs) and breast cancer cells represents an area where the proliferative and immunomodulatory effects of ASCs contribute to an environment that permits neoplastic growth
Additional research needs to be done to further establish the relationship between obASCs’ effect on cancer stem cells and increased metastasis in obesity. Another instance in which obesity contributes to a tumor microenvironment that favors metastasis is through the increased capacity of ASCs from obese patients to differentiate into cancer/carcinoma-associated fibroblasts, or CAFs
Summary
Between 1999 and 2018, the prevalence of obesity in the United States climbed from 30.5 to 42.3% (Hales et al, 2020). We will characterize both adipocytes and adipose stem cells’ role in normal physiology and the breast cancer tumor microenvironment, in the context of obesity. Adipocytes and ASCs represent significant components of breast tissue stroma with important endocrine signaling functions that contribute to both normal breast physiology and pathological processes such as the development of cancer (Wu et al, 2019).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
