Oxidative stress associated to dysfunctional adipose tissue: a potential link between obesity, type 2 diabetes mellitus and breast cancer

Abstract

Diabetes mellitus and breast cancer are two important health problems. Type 2 diabetes (T2DM) and obesity are closely linked with both being associated with breast cancer. Despite abundant epidemiological data, there is no definitive evidence regarding the mechanisms responsible for this association. The proposed mechanisms by which diabetes affects breast cancer risk and prognosis are the same as the mechanisms hypothesised for the contribution of obesity to breast cancer risk. The obesity-induced inflammation promoted by adipose tissue dysfunction is a key feature, which is thought to be an important link between obesity and cancer. Inflammation induces an increase in free radicals and subsequently promotes oxidative stress, which may create a microenvironment favourable to the tumor development in obese persons. Oxidative stress is also proposed as the link between obesity and diabetes mellitus. Therefore, obesity-related oxidative stress could be a direct cause of neoplastic transformation associated with obesity and T2DM in breast cancer cells. This review is focused on the role of obesity-related oxidative stress in the context of chronic inflammation, on the time of breast cancer onset and progression, which provide targets for preventive and therapeutic strategies in the fields of diabetes and obesity-related breast cancer.

Keywords::

• diabetes mellitus
• obesity
• breast cancer
• inflammation
• oxidative stress
• adipose tissue dysfunction

Acknowledgments

The authors express their thanks to Dr. Juan Cueva, Dr. Teresa Curiel, Dr. María Vieito and Dr. Rafael López-López and Dr. Aurelio Sueiro from Complejo Hospitalario Universitario de Santiago de Compostela (Spain) for their clinical assistance in the work performed in the authors’ laboratory.

The authors’ laboratory work is supported by Xunta de Galicia (INCITE 2009), Fundación Mútua Madrileña (FMMA2010), CIBERobn and the INTRASALUD proyect, Instituto de Salud Carlos III (ISCIII) initiatives. AB Crujeiras, on leave from Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria, Complejo Hospitalario Universitario de Santiago (CHUS), is funded by the ISCIII III through a research contract “Sara Borrell” (C09/00365). A Diaz-Lagares was supported by the “Angeles Alvari o-2009” postdoctoral fellowship from the Xunta de Galicia and European Social Fund (ESF) and at present by a “Sara Borrell” postdoctoral contract (CD12/00738), ISCIII.

Declaration of interest

The authors declare report no declarations of interest. The authors alone are responsible for the content and writing of the paper.