J exp Med: Obesity resets immune cells in the breast and promotes tumor formation

May 15, 2019 / BIOON / - smoking has long been the biggest cause of cancer in the United States, but now obesity has become the second largest cause and gradually become the focus of attention A new study by researchers at the University of Chicago found that people with breast cancer, the most common cancer among women, are even more at risk of obesity Breast cancer occurs in adipose tissue Triple negative breast cancer (TNBC) is a very difficult breast cancer to treat None of the three most attractive drug targets - estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 - exist in TNBC cells Image source: the Journal of experimental medicine, author of the study and assistant professor of cancer research at the University of Chicago, Ben may, Dr Lev Becker, said: "these cancers may be particularly aggressive For TNBC patients, treatment options are few and survival rate is very low The incidence rate of cancer in overweight or obese patients tends to increase significantly "Becker said obesity has become a" global epidemic " In the United States, 36% of the population aged 20-39, 43% of the population aged 40-59, and 41% of the population aged 60 and over are affected The United States has the 12th largest obesity rate in the world "The current treatment of breast cancer patients ignores the prevalence of obesity," said Dr Marsha Rosner, Professor Charles B Huggins and co-author of the study at Ben may cancer research "To take this into account, we need to help patients lose weight or identify new drug targets that are effective for obese cancer patients "Unfortunately, once cancer is found, there may not be time to lose weight before treatment "So our bottom line," says Rosner, "is to promote weight loss as a cancer prevention measure, to integrate weight loss into the treatment of breast cancer patients, and to develop specific drug targets that can be used to address the obesity component of the disease "In their paper published in the Journal of experimental medicine on May 3, 2019," metabolically activated diabetes mellitus links obesity to triple negative breast cancer ", Becker, Rosner and colleagues revealed how obesity promotes the biological mechanism of TNBC They point out that obesity reprogrammes macrophages (scavenging leukocytes that phagocytize invaders such as bacteria, viruses or tumor cells) into macrophages that promote inflammation and metabolic activation Instead of fighting against breast cancer, these immune cells promote the development of breast cancer Becker added: "in mice and humans our study involved these metabolically activated fatty tissue macrophages "They accumulate in the fat tissue of the breast They release interleukin-6, an proinflammatory cytokine that promotes tumorigenesis And they depend on obesity to survive IL-6 binds to receptors on the surface of existing cancer cells This could lead to "a more aggressive stem cell phenotype," Becker said These cancer stem cells can promote tumor growth and metastasis, so that they can be transferred to other parts "The higher level of IL-6 in the blood of patients with advanced or metastatic cancer is related to the lower survival rate Obesity is a pathological state, the study's authors write, "that promotes tumorigenesis by creating conditions in multiple tissues that allow tumors to grow "This suggests that chronic inflammation and its effect on tumorigenesis can be reversed by targeted anti-inflammatory therapy or weight loss In fact, the researchers found that inducing obese mice to lose weight by feeding them a healthier, low-fat diet reversed macrophage inflammation and the formation of TNBC tumors in breast fat, even though they were still overweight These findings highlight the potential value of weight loss not only as a preventive intervention, but even after a patient has breast cancer Reference materials: payal Tiwari et al, metabolically activated Adobe tissue macrophases link obsity to triple negative breast cancer, the Journal of Experimental Medicine (2019) Doi: 10.1084/jem.20181616