Lysophospholipids and cancer: current status and perspectives

Circulating phospholipids carrying a single esterified fatty acid, the so-called lysophospholipids, are no,,v considered as mediators of the intercellular communication. Their major members are the lysophosphatidic acid and the sphingosine I-phosphate. two molecules displaying biological activities similar to those of growth factors or cytokines, through a recently identified subfamily of G protein-coupled receptors. They are involved in various biological processes, e.g., brain development and angiogenesis. but the following evidences suggest that these. lipids are also significant actors of tumour development: (i) they stimulate the growth, survival and migration of tumour cells from various origins (ovary, prostate, glioblastoma...); (ii) they are abundant in malignant effusions; (iii) the lysophospholipid-producing enzymes are tumourigenic. Even if it remains necessary to define the role of these "oncolipids" in relationship with oncogenes and tumor suppression, they may well be the mediators of an efficient autostimulatory system of the proliferating and migratory capacities of cancer cells, suggesting that lysophospholipids could represent novel valuable targets for anticancer pharmacology. (C) 2004 Elsevier SAS. Tous droits reserves.