Taking control of key protein helps mice fend off cancer
The spread of cancer is a complex process, and for tumors to grow, the cells of the disease must first find tissue that'll let it thrive. We know that the disease prepares the tissue by acting upon a protein that suppresses the body's natural defences, clearing the way for tumor growth. Now, scientists have worked to take back control of the protein, restoring defences against cancer in laboratory mice.
The protein in question is known as Chitinase 3-like-1, or CHI3L1. It's a common protein, found in a wide range of organisms, acting to help the body fight infections and helping tissue to heal. Unfortunately, it can also be pretty volatile, overreacting to threats, causing harmful immune responses with certain conditions, such as asthma.
An earlier study by the Brown University team, conducted in 2014, had already confirmed that CHI3L1 plays a central role in making tissue more receptive to the spread of tumors.
With the knowledge that the protein represents a fundamental pathway in the progression of the disease, the researchers set out to explain exactly how it promotes tumor growth, while working on a method to intervene in the interaction. To do so, they exposed laboratory mice to cancer cells.
During the investigation, it was found that in the presence of the cancer cells, a second protein called semaphorin 7A caused CHI3L1 to inhibit several anti-tumor responses of the immune system. The researchers also discovered that an antiviral immune pathway known as the RIG-like helicase (RLH) has the ability to counter the cancer cells effect on CHI3L1, but that the cells suppress it by stimulating yet another protein called NLRX1.
This led the team to focus on the RLH pathway, stimulating it with an RNA-like molecule called Poly(I:C). That intervention certainly did the trick in the laboratory mice, with untreated animals developing lung cancer within just two weeks, while those receiving the therapy remaining healthy.
"What we show in this paper is there is a very novel pathway, the RLH pathway, that can actually control the production of CHI3L1," said Dr Jack A Elias. "And when you can control the production of CHI3L1, you can control each of these pathways, and you can control the spread of cancer in these models."
The team's findings are published in full, in the journal Scientific Reports.
Source: Brown University