Nerves connecting up to cancers can trigger them to grow and spread, new research has revealed.
Studying prostate tumours in mice, Claire Magnon and her invade tumors, delivering acetylcholine (Ach), which promotes tumor cell proliferation and egress to lymph nodes through the type 1 muscarinic receptor (Chrm1) expressed on stromal cells. (c) Magnon et al., Science 341, 2013" alt="Nerves control prostate cancer spread" />colleagues at the Albert Einstein College of Medicine in New York found that the cancers responded to chemical signals from nearby nerve cells, leading to enhanced growth, invasion and spread of the tumours.
Blocking these nerve signals, either chemically or by cutting the nerves supplying the prostate gland, dramatically reduced the growth and spread of the tumours in the animals.
The nerves in question are the so-called sympathetic and parasympathetic arms of a network known as the autonomic nervous system, which, in general, has a role in coordinating unconscious processes, including bladder control and prostate secretion.
Tumours seem to provoke these nerves cells to grow into them, although, once connected, the effects on the cancerous tissue of these two nerve supplies are different, the team found.
Sympathetic nerves, which release the nerve transmitter nor-adrenaline, stimulated tumours to grow and establish themselves locally. On the other hand, parasympathetic nerves, which release the chemical acetyl choline, seem to make the tumours more likely to spread.
Consequently, it was almost impossible to establish tumours in mice engineered to lack receptors (called beta-2 and beta-3 receptors) for nor-adrenaline, and animals treated with a drug to block acetyl choline were less likely to show metastatic spread of the tumours to surrounding lymph nodes.
At least some of these effects appear to be down to the surrounding tissue, rather than the cancer cells themselves, because in one series of experiments, the team genetically knocked out the receptors on the cancer cells for acetyl choline. This made no difference to the rate of spread. But knocking out the receptors on the surrounding tissue, leaving the cancer cells able to respond, blocked spread.
To discover whether their findings are clinically relevant, the team also examined 43 samples from human cases of prostate cancer.
High grade tumours and tumours that had spread, they found, were much more likely to have a dense nerve supply compared with lower-grade, less aggressive tumour types.
These findings suggest a new way that cancers might subvert healthy tissue into nurturing them.
Moreover, as the New York team speculate in their paper in Science this week, these findings could also provide the foundation for a new therapeutic approach to the management of prostate cancer...