Bioactive Lipids LPC and LPA are Novel Pro-metastatic Factors and Their Tissue Levels Increase in Response to Radio/Chemotherapy

摘要

Bioactive lipids are fundamental mediators of a number of critical biological processes such as inflammation, proliferation, and apoptosis. Rhabdomyosarcoma (RMS) is common in adolescence with histological subtypes that favor metastasis. However, the factors that influence metastasis are not well appreciated. Here, it is shown that lysophosphatidylcholine (LPC) and its derivative, lysophosphatidic acid (LPA), strongly enhance motility and adhesion of human RMS cells. Importantly, these metastatic-associated phenotypes were observed at physiological concentrations of these lipids which naturally occur in biological fluids. Moreover, the effects of these bioactive lipids were much stronger as compared to known peptide-based pro-metastatic factors in RMS, such as stromal derived factor-1 (SDF-1) or hepatocyte growth factor/scatter factor (HGF/SF). Finally, both LPC and LPA levels were increased in several organs after g-irradiation or chemotherapy, supporting the hypothesis that radio/chemotherapy induces an unwanted pro-metastatic environment in these organs.ImplicationsLPC and LPA play a previously underappreciated role in dissemination of RMS, and suggest that anti-metastatic treatment with specific molecules blocking LPC/LPA activity should be part of standard radio/chemotherapy arsenal.