Obesity is known to increase the risk of developing certain cancers, such as breast cancer and oesophageal cancer; however, the mechanisms underlying this association have been unclear. Now, new research conducted by Bing Li and colleagues indicates that increased levels of adipose fatty acid binding protein (A-FABP) are associated with an increased risk of breast cancer.

STAT3 activation (red) in a primary mammary tumour in an obese mouse. Image courtesy of Bing Li.

“As the two most predominant populations in breast cancer stroma, macrophages and adipocytes have central roles in tumorigenesis and progression of breast cancer; A-FABP attracted our attention due to its abundant expression in both macrophages and adipocytes,” explains Li. By analysing serum samples from women with obesity before and after they underwent Roux-en-Y gastric bypass surgery, the researchers established that circulating levels of A-FABP were increased in conditions of obesity and that levels reduced as BMI declined.

To investigate the link between A-FABP and increased risk of breast cancer, Li and colleagues collected serum samples from 285 women with breast lesions before they underwent diagnostic biopsies. Importantly, they found that circulating levels of A-FABP were elevated in women with obesity who were diagnosed with breast cancer, but not in lean women who received this diagnosis. In addition, experiments in mice fed a high-fat diet to induce obesity showed that ablation of A-FABP did not affect the degree of obesity, but did inhibit tumour growth and development in the mammary tissue. In vitro, Li and colleagues showed that A-FABP treatment resulted in activation of the IL-6–STAT3–ALDH1 signalling pathway and an increase in levels of STAT3-activating cytokines, which increased the stemness and aggressiveness of tumours. “Our research indicates that A-FABP is a new player in breast cancer development,” says Li.

The researchers are expanding their studies in this area, including analyses of whether A-FABP expression in particular subsets of cells are associated with the development and progression of breast cancer. “We believe that these studies will facilitate its potential application in breast cancer diagnosis and immunotherapy in clinical medicine,” concludes Li.