It’s estimated that as much as 90 percent of cancer deaths are due to metastasis - the spread of cancer from the primary organ to other organs in the body. Despite this, scientists are only beginning to unravel the biological underpinnings behind this process.
One of the most recent investigations into this problem focused on the genetic regulation of cancer metastasis. In particular, scientists from the Wellcome Trust Sanger Institute sought to understand what genes influence this process. In so doing, they injected mice with melanomas (skin cancers) and monitored genetic alterations as the tumor metastasized to the animals’ lungs.
In total, the team screened 810 mutant mouse lines. Of these, they identified 23 genes that appeared to directly influence the spread of skin cancer to the lungs. Interestingly, of the 23 genes identified, 19 had not been previously linked to metastasis.
The team then analyzed the list of 23 genes to identify the one that most greatly influences metastasis. They landed on the Spns2 gene, the absence of which led to a reduction in tumor spread to the lungs by four times. Absence of this gene also decreased tumor spread for other types of cancers, including colon and breast cancer.
"Loss of the Spns2 gene causes the greatest reduction in the formation of tumour colonies and represents a novel therapeutic target. We found that mice lacking Spns2 have a different ratio of immune system cells than normal, which seems to prime the immune system to remove cancer. Drugs that target this could help reduce or prevent the spread of tumours through the body,” said Dr. David Adams from the Wellcome Trust Sanger Institute, and the study’s senior author.
Spns2 encodes a protein that transports the S1P lipid, which is involved in the immune system. For the researchers, such evidence ties in immune regulation and cancer events quite nicely. "This work supports the emerging area of immunotherapy, where the bodies' own immune system is harnessed to fight cancer. Drugs could be designed to bind to the S1P transporter, preventing it from working and causing advantageous changes to the immune system. Investigation of further targets in the Spns2 pathway, or other targets identified in this study could help develop potential therapies,” said Dr Anneliese Speak, one of the study’s co-authors.
"This study in mice gives a new insight into the genes that play a role in cancer spreading and may highlight a potential way to treat cancer in the future. Cancer that has spread is tough to treat, so research such as this is vital in the search for ways to tackle this process,” said Dr. Justine Alford, Cancer Research UK's senior science information officer.
Additional sources: Wellcome Trust Sanger Institute, BBC