Targeting just one of the genes – known as Spns2 – led to a three-quarters reduction in the spread of skin cancer tumours, pictured under the microscope,, the experts found
A new biological target for drugs to reduce the spread of tumours in cancer patients has been found by Wellcome Trust Sanger Institute. Published in Nature today, the study with genetically modified mice found 23 genes out of 810 unique genes that either increased or decreased the spread of skin tumour cells to the lungs. Many of these genes also caused an alteration in the immune system, such as changing the bodies’ ability to fight infection. The researchers showed that targeting one of these genes – Spns2 – led to a 3/4 reduction in tumour metastasis.
Removal of the Spns2 gene caused the largest change, reducing spread of tumours to the lungs by approximately four times. The researchers then looked at the effect of this gene on the spread of other cancers, from colon, lung and breast, and showed that taking out Spns2 also reduced the metastasis of these cancers.
Dr David Adams said: “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.”
Before this study, the Spns2 gene was known to affect the immune system, but was not implicated in tumour spread. It codes for a protein that transports a ipid, S1P, which signals to the immune system. Without this transporter protein, the signaling doesn’t work properly and results in changes in the proportion of different immune cells in the body.
Dr Anneliese Speak said: “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.”
Dr Justine Alford said: “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.” http://www.alphagalileo.org/ViewItem.aspx?ItemId=171477&CultureCode=en http://www.nature.com/nature/journal/v541/n7636/full/nature20792.html
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