A treatment preventing cancer metastases may become a reality within a decade, as researchers pinpointed a molecule driving metastasis formation in several cancers, including malignant melanoma.
But the findings also show that the metastatic potential of a cancer may be dependent on what we eat, since the newly identified factor depends on fat to do its work.
The study, “Targeting metastasis-initiating cells through the fatty acid receptor CD36,” was published in the journal Nature.
Researchers at the Institute for Research in Biomedicine (IRB Barcelona) showed that the factor, called CD36, is what differs between metastatic and non-metastatic cancer cells. Adding the factor to tumors with no tendencies to spread made them metastasize.
In addition to melanoma, analyses showed that the factor controls metastasis formation in oral and breast cancer, and likely also in ovarian, lung, and bladder cancer.
“We expect this study to have a big impact on the scientific community and to further advances in metastasis research, and we hope to be able to validate the potential of CD36 as an anti-metastasis treatment. Things like this don’t happen every day,” Dr. Salvador Aznar-Benitah, head of the Stem Cell and Cancer Lab at IRB Barcelona and senior author of the study, said in a news release.
“We can now obtain metastatic cells in the laboratory. This will allow us to trace them and to study, for example, their distribution in the tumor, where they anchor when they leave it, or why they are so sensitive to fat, among other questions,” added Gloria Pascual, the study’s first author.
Fat driving cancer spread
Since CD36 is a fat-processing protein, researchers decided to have a look at how fat intake impacts metastasis potential. They fed a group of mice a diet containing about 15 percent more fat than normal. They then injected tumor cells into the animals, comparing them to normally fed mice.
While the increase in fat intake was seemingly modest, the effects were not. About 30 percent of the mice on a normal diet developed metastases, while in mice eating more fat, the number was 80 percent. These mice also had more and larger metastases.
In another experiment, the team exposed lab-grown cancer cells to palmitic acid — a type of fat present in palm oil, used in many types of processed foods. After feeding the cells palmitic acid for two days, the cells were injected into mice. The cancer spread in all mice that received the palmitic acid-treated cells, while only 50 percent of mice injected with untreated cancer cells developed metastases.
“More studies are needed to unravel this intriguing relationship between diet and metastasis, above all because industrialized countries are registering an alarming increase in the consumption of saturated fats and sugar,” Aznar-Benitah said.
“Fat is necessary for the function of the body, but uncontrolled intake can have an effect on health, as already shown for some tumors such as colon cancer, and in metastasis, as we demonstrate here,” he added
A path to intervention
But the study is not all bad news. Researchers tested whether it would be possible to prevent cancer spread by blocking CD36 with antibodies, and the findings were clear. Blocking the molecule before cancer had spread completely deprived the cancer of its ability to metastasize.
Also, in mice that already had developed metastasis, the treatment was beneficial; in 20 percent of the animals, the metastases disappeared. In the remaining animals, the numbers and sizes of the metastases were reduced by 80 percent to 90 percent. So far, the team did not observe any severe side effects of the treatment.
Researchers at IRB Barcelona have partnered with MRC Technology in the United Kingdom to develop an antibody treatment to block CD36 for preventing metastasis formation in humans. If the venture is successful, such a drug could reach the market within five or 10 years.