Triple-negative breast tumors may recruit nerves via macrophage BDNF signaling

University of Oklahoma researchers report that triple-negative breast tumors may recruit nerves that support growth and treatment resistance by turning macrophages into messengers that release brain-derived neurotrophic factor (BDNF). Networks of nerves have been observed in many solid tumors, but their origin has remained uncertain. Research published in Cell Death & Differentiation traces the process in triple-negative breast cancer, a form of the disease that is particularly difficult to treat. The investigation focused on macrophages, immune cells that normally fight infections and repair damaged tissue. Triple-negative breast tumors draw these cells into their surroundings, where the macrophages release BDNF, a protein best known for supporting nerve cells in the brain. Inside breast tumors, the same signal appears to attract nearby nerves that help the cancer grow and withstand treatment. Maureen Cox, Ph.D., an assistant professor in the Department of Microbiology and Immunology at the OU College of Medicine and a research member of OU Health Stephenson Cancer Center, said macrophages are the critical source for drawing nerves into the tumor and that they facilitate a negative function in this breast-cancer setting even though they typically play a positive role in the body. The mechanism suggests a strategy that does not attack cancer cells directly but interrupts communication between macrophages and tumor-supporting nerves. Cox and colleagues tested the approach in mice with a drug that blocks BDNF signaling. The treatment prevented nerves from entering the tumors and significantly reduced tumor growth. Cox said the drug is already on the market and that nerves appear immunosuppressive, so stopping nerve growth might boost the immune response against the cancer. To check whether the pathway may operate in people, the team examined data from patients with triple-negative breast cancer. Higher levels of macrophages and BDNF within tumors were associated with poorer survival. Cox plans to investigate how nerves promote tumor growth, including possible roles in encouraging blood vessels that supply oxygen and nutrients and in providing routes for tumor cells to leave the primary site. She also intends to test the same intervention in high-grade ovarian cancer. The research was supported by National Institute of General Medical Sciences awards from the NIH.