JESPER KLAUSEN/SCIENCE PHOTO LIBRARY
Cancer cells that travel through lymphatic fluid – which flushes infection-fighting cells through the body and helps remove cellular debris – may be more likely to seed distant growths because they pick up “coats” made of monounsaturated fatty acids that help protect them from damage, allowing them to survive long enough to form new tumours.
“Many people have been studying circulating cancer cells in the blood, but almost nobody has been studying cancer cells as they migrate through lymphatics,” says Sean Morrison at University of Texas Southwestern Medical Center. The reason, he explains, is pretty simple: blood samples are much easier to obtain than lymphatic ones.
It usually takes years for tumours to spread to distant sites in the body, or metastasise, mainly because most of the cells die while they’re migrating through the blood. In previous work, Morrison and his team suggested that oxidative stress, a process by which free oxygen radicals can damage fatty cell membranes, was killing off most of these cells. But it wasn’t clear why some are able to survive this.
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To find out, Morrison and his team injected dyed human melanoma cells into the veins or lymph nodes of 520 mice and then traced how those cells moved through the body. They found that more cancer cells survived in the lymph than in the blood, and that they were more likely to seed distant tumours. Those in the blood were more likely to have undergone high levels of oxidative stress and died.
Then, the team isolated cancer cells from the blood and the lymph nodes to better understand why the two behaved differently. Within the membranes of the cancer cells in lymph nodes, the researchers found higher levels of oleic acid, a monounsaturated fatty acid. Their cellular counterparts in the blood that skipped the stop in the lymph nodes had membranes made up mainly of polyunsaturated fatty acids, which are more prone to damage from oxidative stress.
The oleic acid in the cells exposed to lymphatic fluid diluted the polyunsaturated fats and shielded them from oxidative damage when they later travelled through the blood to distant parts of the body, says Morrison.
He says this gives researchers another target in the fight to prevent cancer progression in patients. In addition to drugs that might disrupt this protective membrane, Morrison and his team are testing the effects of feeding mice a “cheeseburger diet”, heavy in fats that could keep the membrane vulnerable to damage and slow cancer progression.
Journal reference: Nature, DOI: 10.1038/s41586-020-2623-z
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