Stopping Cancer Tumors “Hijacking” the Genetic Program Used by Developing Nerves

"We are still only early in the research, but this opens up exciting opportunities to fight cancer in the body in a completely new way," says Sara Wilson, associate professor of neurobiology at the Department of Integrative Medical Biology at Umeå University.

In cancer, there is an interaction between tumours and nerves. You could say that the tumour talks to the nervous system. The idea of a study at Umeå University is that by interpreting this "conversation", it will later be possible to find ways to break it and thus slow the cancer down or reduce the risk of it spreading.

All organs in the body have nerves, which act as a pathway system that delivers information between the organs, the brain and the rest of the body. An interesting fact is that many different types of tumours have an increased density of nerves within and around the tumour, compared to healthy organs. It shows that the cancer has caused nerves to grow and reorganize. Normally, the body's nerve map is created very early, already when we are embryos in the mother's womb. In healthy people, the ability of the nerves to grow and reorganize is limited, but cancer seems to be able to dislodge this. The question has been why.

Previous research has shown that tumours with high density of nerves grow faster, become larger and spread to other parts of the body and form metastases through the tumour nerves. They use the tumours nerves like a road to travel out of the tumour. This process is called peri neural invasion, PNI. The goal of the Umeå researchers' study was to decipher the molecular language used in these interactions between tumours and nerves.

The researchers found that in the tumours there was a group of genes centred around the molecular networks normally used by developing nerves. These are the same genes/molecular networks that, in the embryo, help the nerve grow and eventually reach all parts of the body. Previous studies by the Umeå researchers have shown that as the nervous system forms in the embryo, the ‘axons’, of some nerve cells are used by other nerve cells to move to the right place within the nervous system. The axons create a "road map" so that other cells find their way. The Umeå researchers together with researchers throughout the world have also previously shown how the location and direction of the axons from the nerve cells is controlled by networks of certain genes.

The new finding was that the different cancers had their own variants of a set of genes that normally control the nerves road map, which could be the key to how the nerves are tricked into redrawing their pathways. The cancer seems to reactivate genes that in healthy people are active during the embryo stage where they control the development of the nervous system, but which in cancer instead seem to send signals that favour the growth and spread of the tumour.

"The tumours seem to outsmart the genetic programmes of the nerves for their own destructive purposes. Continued research can hopefully provide answers to how we, in turn, can outsmart the tumours to prevent them from using genes to control the nervous system," says Sara Wilson.

Reference: González-Castrillón LM, Wurmser M, Öhlund D, Wilson SI. Dysregulation of core neurodevelopmental pathways—a common feature of cancers with perineural invasion. Front Genet. 2023;14:1181775. doi: 10.3389/fgene.2023.1181775

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