Written by Aaron Khemchandani, Science Writer.
New research has revealed crucial insights into how cancers spread around the body, and these discoveries could heavily influence future therapeutic research.
Exploiting healthy cells
A team of researchers at the Cancer Research UK (CRUK) Cambridge Institute have revealed that cancer cells ‘hijack’ a process used by normal cells to spread around the body, revolutionizing how we think about tumour metastasis. The scientists, publishing their findings in the journal Nature Genetics, uncovered that blocking the sodium leak channel non-selective protein (NALCN) in mice with cancer triggers metastasis.
Researchers administered a NALCN channel blocker to mice with either gastric, intestinal or pancreatic adenocarcinomas. Besides observing impacts on tumour metastasis, the team also noted marked increases in the numbers of circulating tumour cells (CTCs) in the blood; given the influence of NALCN on cancer spread, this was expected as CTCs are normally shed from tumours into the bloodstream prior to metastasis.
However, the scientists also discovered that metastatic processes are not just limited to cancer. To their surprise, removing NALCN from healthy mice without cancer caused healthy cells to leave their tissue of origin and migrate to assimilate into the tissues of other organs.
A shocking discovery
The team noticed, for example, that healthy pancreatic cells migrated to the kidney where they became healthy renal cells. This observation is significant, as it suggests that metastasis is not an abnormal process limited to cancers as previously thought. Rather, it appears to be a regular process employed by healthy cells that has been exploited by cancers to move to other areas of the body and metastasise.
This research identifies NALCN as a key regulator of both cancer metastasis and healthy cell migration, which in turn make it a potential target for cancer therapeutics. The study’s lead researcher, Dr. Eric Rahrmann, said: “We are incredibly excited to have identified a single protein that regulates not only how cancer spreads through the body, independent of tumour growth, but also normal tissue cell shedding and repair. We are developing a clearer picture on the processes that govern how cancer cells spread, and can now consider whether there are likely existing drugs which could be repurposed to prevent this mechanism from triggering cancer spreading in patients.”
Impacts beyond cancer
The protein is a sodium leak channel expressed mainly throughout the central nervous system, and it sits across cell membranes where it controls the amounts of sodium that enter the cells. Interestingly, previous research has linked NALCN function to a host of diseases; mutations in the NALCN gene have been identified in patients with infantile neuroaxonal dystrophy, for example, although why the channel seems to be so directly involved in cancer spread is not yet certain.
A huge leap forward
The identification of NALCN as a regulator of both tumour metastasis and normal cell migration poses a number of implications for future therapeutic research. As such, these findings represent huge progress in our understanding of cancer metastasis.
Group Leader for the study and Director of the CRUK Cambridge Centre, Professor Richard Gilbertson, identified the research as “among the most important to have come out of my lab for three decades,” adding “if validated through further research, this could have far-reaching implications for how we prevent cancer from spreading and allow us to manipulate this process to repair damaged organs.”