By Emma Yasinski
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 tumours because they pick up “coats” made of monounsaturated fatty acids that help protect them from damage, allowing them to survive long enough 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 in the US. The reason, he explains, is pretty simple. Blood samples are much easier to obtain than lymphatic ones.
Usually, cancer cells are inefficient at metastasising. It takes years for tumours to spread to distant sites in the body, 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 still able to survive the stress.
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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 there were more cancer cells in the lymphatic fluid than the blood, and that the cells in the blood had undergone high levels of oxidative stress.
Within the membranes of cancer cells found in lymph nodes, the team 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 primary of polyunsaturated fatty acids, which are more prone to damage from oxidative stress.
The oleic acid diluted the polyunsaturated fats and shielded the cells from oxidative damage as they traveled 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 polyunsaturated fats that they hope will slow cancer progression.
Journal reference: Nature, DOI: 10.1038/s41586-020-2623-z
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