New research published in Nature may have identified one way cancer cells metastasize to spread and resist treatment. The study showed how a cancer protein interacts with dietary fat to facilitate metastasis and may pave the way for new cancer therapies.
The discovery came about in phases. First, the researchers identified the role that the CD36 protein plays in cancer metastasis. CD36 allows cells to take up lipids from their environment. They analyzed metastatic and nonmetastatic cells taken from melanoma and oral, ovarian, bladder, lung, and breast cancer samples and found that the metastatic cells overexpressed CD36. Additionally, when CD36 was added to nonmetastatic cells, they began to metastasize.
The researchers noted that they have not confirmed the findings in all tumor types, but they believe it is the first identified general marker of metastasis.
Expanding on their findings, the researchers explored whether CD36 could use dietary fat to increase cancer metastasis in a mouse study. They injected two groups of mice—one fed a high- fat diet and a control group fed a normal diet—with human oral cancer cells. Those on the high-fat diet had greater metastasis and formed larger tumors.
They then treated human oral tumor cells with palmitic acid, a saturated fatty acid in vegetable and animal fats, and injected those cells into a different set of mice, all of which were fed a normal diet. All of the mice who received the palmitic acid-treated cells experienced cancer metastasis, compared to only half of the mice who received untreated cells.
Finally, the researchers developed CD36-blocking antibodies and administered those to mice with human oral cancer. The antibodies completely prevented metastasis in mice whose cancer hadn’t spread yet. In those that did have metastasis, the antibodies reduced the number of metastatic tumors by 80%–90% and reduced the size of tumors that did metastasize. In 20% of the mice, the metastatic tumors were eradicated completely.
The researchers are developing drugs to target and block CD36, and the results will need to be tested in well-conducted clinical trials.
Pascual, G., Avgustinova, A., Mejetta, S., Martín, M., Castellanos, A., Attolini, C.S., . . . Benitah, S.A. (2017). Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature, 541. doi:10.1038/ nature20791