The high mortality of @entity320 is caused by rapid spread of @entity5 cells, which occurs unusually early in @entity5 evolution. Unlike most solid @entity5 , @entity121 rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive @entity320 cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real @entity5 . In a chamber-based assay for @entity320 dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive @entity6722 rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all @entity5 stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor @entity25068 . LPA induces @entity6722 of remarkable accuracy, and is both necessary and sufficient for @entity6722 and invasion in 2-D and 3-D assays. Growth factors, often described as @entity5 attractants, cause negligible @entity6722 themselves, but potentiate @entity6722 to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of @entity320 in vivo, confirming the physiological importance of our results. We conclude that LPA @entity6722 provides a strong drive for @entity320 cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the @entity5 and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the @entity5 growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient.

XXXX cells break down LPA to establish local gradients that drive chemotactic dispersal.

@entity6722 :: ('MESH:C565534', 'Disease') :: ['chemotaxis'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer', 'tumours', 'tumour'] @entity25068 :: ('1902', 'Gene') :: ['LPAR1'] @entity121 :: ('MESH:D009135', 'Disease') :: ['thickness'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma', 'melanomas']
@entity320 :: (MESH:D008545,Disease) :: ['Melanoma']
