Cancer Genes That Promote Metastasis Identified, Paving The Way For Therapeutics To Prevent Cancer Spread
-promoting genes MYC
co-opt immune system cells to enable cancer
cells to spread, but blocking a key step in this process can help prevent the disease from developing.
These research findings, published today in eLife
, may help clinicians to identify cancer
patients at risk of metastasis
, a process where cancer
cells spread to other parts of the body. They may also inform the development of new strategies to prevent or treat metastasis
Lead author Dr Renumathy Dhanasekaran, a Ph.D. student in the Division of Gastroenterology and Hepatology at Stanford University, California explained to Thailand Medical
News, "Most cancer
-related deaths are caused by metastasis
, but there are currently no treatments available to stop it. The main goal of our research is to understand how cancer
and use that information to identify targeted therapies that may prevent it."
Dr Dhanasekaran and her colleagues genetically engineered mice to express both MYC
and found that these two major cancer
led to metastases
. They also saw that the cancer
cells produced inflammation-promoting molecules Ccl2 and Il13, which attract immune cells called macrophages and make them more tumour-cell friendly. This makes it easier for the cancer
cells to migrate to new areas of the body.
The research team next showed that exposing mice with liver cancer
caused by MYC
alone to Ccl2 and Il13 causes metastasis
. But blocking this specific combination of cytokines appeared to hinder the process.
To confirm if the two genes
also contributed to metastases
in humans, the scientists analysed 10,000 samples of tumours collected from humans with 33 different types of cancer
. They found that patients with MYC
were less likely to survive, produced more Ccl2 and Il13, and had more macrophages in their tumours.
Senior author Dr Dean Felsher, Ph.D., Professor in the Division of Oncology at Stanford University added, "Interestingly, MYC
have previously been shown to cooperate in a positive way to modulate inflammation during embryonic development. These microenvironment changes are needed to enable mesodermal cells to migrate to their destination. But in multiple human cancers
, both MYC
are over-expressed, and we suggest that they in turn cause tumour invasion by 'hijacking'
this embryonic cell migration program."
Lastly, the research team monitored Ccl2 and Il13 levels in 25 patients with liver cancer
and 10 control patients with cirrhosis. They found that only the patients with liver cancer
had elevated levels of the two molecules and, of this group, those with higher levels of Il13 were more likely to have aggressive tumours.
Dr Felsher concludes, "These results suggest that patients with more aggressive cancers
will likely have higher levels of Ccl2 and Il13 cytokines in their blood. Testing for these molecules in future could help identify those who may benefit from combination therapies that target them."
Reference: Renumathy Dhanasekaran et al, MYC and Twist1 cooperate to drive metastasis by eliciting crosstalk between cancer and innate immunity, eLife (2020). DOI: 10.7554/eLife.50731