Nerve signaling encourages tumor growth

Nerves inside prostate tumors release chemical compounds that stimulate the growth of blood vessels feeding the cancer cells, according to a study in mice (Science 2017, DOI: 10.1126/science.aah5072). Therapies that block this type of chemical signaling could help slow the growth of tumors, the researchers say. In 2013, Paul S. Frenette of Albert Einstein College of Medicine and colleagues found that destroying nerves in tumors halted the progression of prostate cancer in mice. These specific nerves send signals by releasing the neurotransmitter noradrenaline, which binds to the β₂-adrenergic receptor (ADRβ₂). In the new study, the researchers determined that noradrenaline activates ADRβ₂ in the endothelial cells of the mice’s blood vessels. Once activated, ADRβ₂ promotes the formation of new blood vessels—a process called angiogenesis—by ensuring the cells continue to metabolize glucose through glycolysis. When the researchers knocked out the gene for ADRβ₂ in the endothelial cells, the cells used an alternative metabolic pathway called oxidative phosphorylation, and as a result, there was little blood vessel growth. Frenette points out that some anticancer therapies targeting angiogenesis have not had long-term success against prostate tumors. He proposes studying the effectiveness of targeting angiogenesis along with nerve signaling with β-blockers, which inhibit ADRβ₂.