The Role of Bioactive Lipids in Cancer Metastasis

thescientist | Although metastasis is the leading cause of death among people with cancer, for the most part, researchers are stumped about which molecular signals allow malignant cells to leave primary tumors and start new ones. Two studies published in Nature this month highlight roles in metastasis for an unexpected group of molecules—lipids.

“For many years, we were studying peptides and proteins,” said Mariusz Ratajczak, a cell biologist at the University of Louisville who was not involved in the studies. “Now we are coming to bioactive lipids.”

In the first study, published January 5, researchers at the Institute for Research in Biomedicine (IRB) in Barcelona reported that, in mice, human oral cancer cells that are most likely to migrate from primary tumors are marked by the surface protein, CD36—a scavenger receptor that binds fatty acids. The researchers initially identified the cells by examining genes upregulated in non-cycling tumor cells, finding increased expression of genes involved in lipid metabolism, transport, and storage—all processes downstream of CD36.

When the researchers knocked down CD36 with short hairpin RNA before the injecting oral cancer cells into mice, they prevented the cells from seeding metastatic tumors in the lymph nodes of 80 percent to 100 percent of the animals without significantly changing the frequencies of primary tumors. “What’s really cool here is that they showed that CD36 wasn’t necessary for self-renewal, but was necessary for dissemination and metastasis,” said Justin Lathia, a cell and molecular biologist at the Cleveland Clinic who was not involved in the work. This study, he added, demonstrates that metastatic cells don’t have to be cancer stem cells.

It also suggests that metastatic cells may have their own unique metabolic regulation. The IRB team demonstrated that feeding mice a high-fat diet increased the size and number of metastatic lymph node tumors. This effect was lost when CD36 was knocked down. The researchers generated the same effect when they pretreated the cancer cells in culture with a dietary fatty acid called palmitic acid. Lathia note that while this finding could provide insight into the link between obesity and cancer, “human diets are far more complex than what we have here.”