Chemoresistance : intricate interplay between breast tumor cells and adipocytes in the tumor microenvironment

Mentoor, Ilze ; Engelbrecht, Anna-Mart ; Van Jaarsveld, Paul J. ; Nell, Theo A. (2018-12-11)

CITATION: Mentoor, I., et al. 2018. Chemoresistance : intricate interplay between breast tumor cells and adipocytes in the tumor microenvironment. Frontiers in Endocrinology, 9:758, doi:10.3389/fendo.2018.00758.

The original publication is available at

Publication of this article was funded by the Stellenbosch University Open Access Fund.


Excess adipose tissue is a hallmark of an overweight and/or obese state as well as a primary risk factor for breast cancer development and progression. In an overweight/obese state adipose tissue becomes dysfunctional due to rapid hypertrophy, hyperplasia, and immune cell infiltration which is associated with sustained low-grade inflammation originating from dysfunctional adipokine synthesis. Evidence also supports the role of excess adipose tissue (overweight/obesity) as a casual factor for the development of chemotherapeutic drug resistance. Obesity-mediated effects/modifications may contribute to chemotherapeutic drug resistance by altering drug pharmacokinetics, inducing chronic inflammation, as well as altering tumor-associated adipocyte adipokine secretion. Adipocytes in the breast tumor microenvironment enhance breast tumor cell survival and decrease the efficacy of chemotherapeutic agents, resulting in chemotherapeutic resistance. A well-know chemotherapeutic agent, doxorubicin, has shown to negatively impact adipose tissue homeostasis, affecting adipose tissue/adipocyte functionality and storage. Here, it is implied that doxorubicin disrupts adipose tissue homeostasis affecting the functionality of adipose tissue/adipocytes. Although evidence on the effects of doxorubicin on adipose tissue/adipocytes under obesogenic conditions are lacking, this narrative review explores the potential role of obesity in breast cancer progression and treatment resistance with inflammation as an underlying mechanism.

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