‘Breadcrumb trail’ helps melanoma spread

Just like Hansel and Gretel followed the trail of breadcrumbs to the witch’s house, melanoma cells follow the trail of a naturally-occurring molecule allowing it to metastasise in the body. Melanoma cells are able to move through the body using a fatty chemical lysophosphatidic acid (LPA), a team from the Cancer Research UK Beatson Institute at the University of Glasgow found. "Our exciting findings show that skin cancer cells create their own 'green light' signal to start spreading, and are lured to travel around the body by a trail of these fatty molecules,” said Professor Robert Insall, Cancer Research UK scientist at the Beatson Institute. Working in both cancer cell lines and mice, scientists showed that tumour cells start their journey by breaking down LPA. Once nearby levels are depleted they move out of the tumour in search of more, creating the breadcrumb trail which leads to the bloodstream and new sites in the body. Scientists examined signals during the spread of melanoma cells using 2D assays and described their findings, published in PLOS Biology, as surprising since the cells consistently spread outwards from the well in which they started. This resembles the behaviour of real melanoma; the cells moved from their original well with unprecedented accuracy, they write, perceiving a directional cue. The scientists suggest that chemotactic signalling mechanism causes this outward spreading; the cells generate a chemotactic gradient which drive dispersal away from themselves. Unlike other cancers which are normally sticky, melanoma cells are primed to move right from the start, so as soon as they have taken directions from LPA they start to spread. This makes it difficult to treat because it spreads quickly and aggressively. "The next step will be to find how the melanoma cells break down the LPA molecules to see if this sparks ideas for new ways to stop the cancer from spreading,” said Insall, lead author of the paper. “At the moment our research is still in early stages but we hope this could help doctors to make sure this cancer doesn't spread." Melanoma Cells Break Down LPA to Establish Local Gradients That Drive Chemotactic Dispersal