The metastasis of cancer cells using neural signalling pathways – a new discovery with promise of better diagnostic and treatment.

By Mark Markov

By all accounts, cancer is the emperor of all maladies, the greatest and most imminent challenge to modern medicine. Whilst the great variety of cancer is evidenced in the diversity of physical origin, aggression, solubility and treatability, a list which barely begins to encompass cancer’s wild and unpredictable variations, there is a common thread which ties together each and every instance of cancerous tumour: their penchant for molecular deceit. Cancer cells are expert hijackers, which can, much like viral cells, take over the biological systems and data centres of their hosts, to grow, survive and replicate aggressively.

Scientists at Rockefeller University have very recently discovered (Tavora, 2020) that certain breast and lung tumours use the electrical signalling pathways which are used by neurons to metastasize, meaning they break free from a local tissue group or organ and create new cancerous growths in other organs around the body. Scientific consensus was that cancerous tumours used the cardiovascular system and lymphatic system (blood vessels and lymph nodes respectively) merely to break off and travel around the body; however, researchers at RU have discovered biological mechanisms by which cancer cells enlist the of blood vessels to help them gain access to corresponding nerve signals, allowing them to break free from their primary site of growth and into the bloodstream. This discovery opens up a new frontier on which scientists can help fight serious outbreaks of aggressive cancers. 

Some years ago, lead researcher, Sohail Tavazoie observed that not only were aggressive tumours hijacking nearby vasculature (blood vessels) to gain access to the body’s supply of oxygen and nutrients, but also that cancers that recruited more nearby vessels were the ones especially prone to metastasis. However, the causal mechanism behind this observation remained a mystery to Tavazoie and the wider scientific community. That was, until new research headed by Bernardo Tavora’s research team at the Rockefeller University picked up where Tavazoie had left off      

Tavora’s new discovery began with the hypothesis that ‘cells in the inner lining of blood-vessels send a signal that instructs cancer cells within the primary tumor to metastasize’. However, to reach a convincing and meaningful scientific conclusion, Tavora would go on to employ an array of genetic, molecular, and biochemical research techniques in tandem. Namely, this involved the utilization of TRAP (short for Translating Ribosome Affinity Purification), which is a method of studying gene expression making a large impact in the field of medical sciences. In 2015, for example, it was used to study the ageing process in neurons and get incredibly precise molecular characterizations of neuronal species to help find a modulator of Huntington’s Disease, a prolific degenerative condition expressed during later life. 

In the same way, TRAP was used in this scenario to observe very minor differences between mostly similar cells and the proteins produced by them. Tavora was eventually able to isolate a protein usually produced by neurons, Slit2, and explain its presence in the cancer cells they were studying. 

This was immediately telling, as Slit2 is used routinely by the nervous system to help guide nerve-cell extensions as they travel from one part of the brain to the other. It has also been proven to regulate connectivity in neurons amongst worms. 

The researchers then reached a conclusion about the breast and lung cancer cells that they were observing. These cells were using a very delicate and fine-tuned mechanisms to manipulate surrounding blood cells into releasing just enough Silt2 to help the cancer cells start migrating. 

Much like viruses, with their viral RNA, cancer cells about to metastasize activate normally dormant DNA to produce double stranded RNA (dsRNA) which acts as a sort of signal to trigger movement out of the primary tumor and into the blood, to other organs around the body. 

The discovery of the role of Slit2 in metastasis has broad and compelling implications for the treatment and monitoring of cancer. These Silt2 proteins, present in areas where they should not be, could prove effective indicators of cancerous tumours that are about to metastasize, allowing doctors to intervene before it is too late. There is also a more far-fetched, but definitely realizable scenario in which inhibiting the receptors of Silt2 could spawn a new branch of novel cancer drugs.

Overall, this study, published in September 2020, provides a very hopeful and interesting outlook on the treatment of cancer, in the aftermath of the coronavirus outbreak which is driving a massive boom in mortality and incidence of all cancers due to mass disruption in screening, diagnosis and treatment. 

To learn more around the following topics, I recommend the following resources:

To access the journal article:

Bernardo Tavora, Sohail F. Tavazoie. Tumoural activation of TLR3–SLIT2 axis in endothelium drives metastasis. Nature, 2020; DOI: 10.1038/s41586-020-2774-y

To learn more about translating ribosome affinity purification:

https://www.nature.com/scitable/blog/bio2.0/the_trap_technique_gets_back/ 

To learn more about cancer and its impacts, I highly recommend ‘The Emperor of All Maladies’ by Siddhartha Mukherjee:

https://www.waterstones.com/book/the-emperor-of-all-maladies/siddhartha-mukherjee/9780007250929 

To read more about cancer post-covid you can access this publication: 

https://www.carnallfarrar.com/coronavirus/cancer-post-covid-impact-outcomes-and-next-steps