Tumors alter their metabolism in order to spread more quickly: Study

According to a new study, cancer cells can disrupt a metabolic pathway that breaks down fats and proteins in order to increase the levels of methylmalonic acid, a byproduct that promotes metastasis.

“Nature Metabolism” was the journal that published the research. Scientists have discovered a new approach to understanding how tumours metastasize, or spread to other tissues, as well as new ways to stop cancer from spreading by targeting the process.

According to the new findings, metastatic tumours suppress the function of a crucial enzyme in propionate metabolism, the process by which cells digest specific fatty acids and protein components. The generation of methylmalonic acid is increased when the enzyme is suppressed (MMA).

“A lot of work has been focused on primary tumour initiation and growth or examining the metastatic tumour, but going from the primary tumour to the metastatic tumour, that transition has not been studied very extensively,” said co-senior author Dr. John Blenis, the Anna-Maria and Stephen Kellen Professor in Cancer Research, professor of pharmacology and associate director of the basic science of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

Dr. Blenis and his colleagues have been studying the metabolic changes that cells go through during the metastatic transition for several years in order to close that gap. That research previously discovered that as people get older, their systems create more serum MMA (the source of which is unknown) and that greater MMA levels lead to poorer cancer outcomes. However, because healthy cells also make MMA, Dr. Blenis’s team investigated the metabolite’s cancer-related actions in greater depth in the latest study.

Dr. Vivien Low, a postdoctoral fellow in Dr. Blenis’ group, said, “Cancer cells can hijack the pathway that creates methylmalonic acid, and this forms a feed-forward cycle that pushes cancer growth towards more aggressive and metastatic types.”

Dr Ana Gomes and Dr Didem Ilter, the two co-first authors, were postdoctoral fellows in the lab at the time of the study. Dr. Gomes is currently a faculty member at H. Lee Moffitt Cancer Center & Research Institute, while Dr. Ilter is a research scientist.

The study adds to a growing body of evidence suggesting particular metabolic products, known as oncometabolites, have a role in cancer progression and metastasis. While the latest study focused on multiple breast cancer models, Dr. Low said the team is now looking into other types of cancer cells to see if similar mechanisms are at work. Scientists are also looking for new strategies to combat the problem.

“Metastasis is responsible for about 80 to 90 per cent of cancer-related mortality, so if we can predict when someone has the potential to develop metastatic tumours or treat those metastatic tumours that might have this pathway up-regulated, then we might have a very effective, novel therapy,” Dr. Blenis said.