As our bodies convert food into energy, they produce debris that accumulates as we age. New research shows that one of these metabolic throwaways plays a potentially deadly role in the development of cancer.
The finding adds a body of knowledge about the ways in which the aging process develops our chances of fatal cancers, but also offers potential possibilities for blocking metastatic tumors.
The study, published Wednesday in the Journal of Nature, grew out of work on metastasis, the process by which cancer cells detach from an initial tumor and previous new tumors elsewhere in the body.
Observations of metastatic cells reveal something intriguing – a high level of something called methylmalonic acid (MMA), a metabolic byproduct that seems to accumulate as we age.
To investigate whether MMA may play a role in metastasis, the researchers examined how tumor cells from lung and breast cancer behaved when exposed to blood samples taken from people 30 years and younger, 60 years and older.
In 25 of the 30 blood samples from younger donors, the cancer cells showed no change, but in 25 of the 30 older blood samples, the cells began to show different characteristics.
They developed increased “migration and invasion capacity”, as well as resistance to two drugs that were often used to treat cancer, the study found.
When the cells were injected into mice, they produced metastatic tumors in the lungs.
So how does MMA induce these changes in cancer cells? The key seems to be in some sort of reprogramming that a gene called “SO switches”.
Preliminary research has shown that SOX4 stimulates cancer cells to become more aggressive and are envious of metastasis.
– ‘A lot to do’ –
To test whether it was indeed SOX4 that altered the qualities of the cancer cells, the team blocked the expression of the gene, and found that MMA no longer appeared to have the same effect.
Blocking SOX4 stopped the process by which the cancer cells were able to resist two cancer treatments.
“This discovery is the beginning of a lot of research in many different directions,” said John Blenis, a professor of pharmacology at Weill Cornell Medicine, who led the research.
“But our great hope is that we can eventually develop therapies to reduce MMA levels and thereby reduce cancer mortality,” Blenis said in a statement issued by Weill Cornell Medicine.
There are still many unanswered questions, including why MMA accumulates with age, and whether the mechanism that the researchers observed in the blood samples and in mice would be the same in humans.
The blood samples used were also all taken from men, and among the avenues Blenis hopes to further investigate is whether MMA accumulation has the same effects in women.
“It’s a brand new discovery, and we still have a lot to do to follow it up,” Blenis said.
But there are already some promising potential ways that the findings could influence treatment.
MMA accumulation is linked to high-protein diets, so it is possible that a low-protein diet may respond better to cancer patients.
In theory, drugs that reduce MMA levels may also play a role, potentially reducing the aggressive spread of cancers in patients.
sah / rma
