LPP3, LPA and self-generated chemotactic gradients in biomedical science

Chemotaxis is a major driver of cancer spread, but in most cases we do not know where gradients of attractant come from. In the case of melanoma, chemotaxis to LPA is an important driver of metastasis, and the gradients are made by the tumour cells themselves, by locally breaking down ambient LPA. We have now made a general assay for self-generated chemotaxis, and used it to show that the enzyme LPP3 is responsible for breaking down LPA and thus creating the gradients. Further analysis shows LPP3 is important in several invasion assays, in particular 3D ones in which cells spread outwards through matrix. The new assays will illuminate where physiological self-generated gradients occur; we believe they will be common throughout biology and pathology.