title: Bioactive lipids, LPC and LPA, are novel prometastatic factors and their tissue levels increase in response to radio/chemotherapy.
abstract: Bioactive lipids are fundamental mediators of a number of critical biologic processes such as inflammation, proliferation, and apoptosis. Rhabdomyosarcoma (RMS) is common in adolescence with histologic 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 physiologic concentrations of these lipids, which naturally occur in biologic fluids. Moreover, the effects of these bioactive lipids were much stronger as compared with known peptide-based prometastatic factors in RMS, such as stromal-derived factor-1 or hepatocyte growth factor/scatter factor. Finally, both LPC and LPA levels were increased in several organs after γ-irradiation or chemotherapy, supporting the hypothesis that radio/chemotherapy induces an unwanted prometastatic environment in these organs.
  
  
  CONCLUSIONS
  LPC and LPA play a previously underappreciated role in dissemination of RMS and suggest that antimetastatic treatment with specific molecules blocking LPC/LPA activity should be part of standard radio/chemotherapy arsenal.
authors.affiliation: Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Schneider
authors.affiliation: Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
authors.forename: Zachariah Payne
authors.initials: ZP
authors.lastname: Sellers
authors.affiliation: Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, Kentucky.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdel-Latif
authors.affiliation: Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, Kentucky.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.affiliation: Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky. Department of Physiology Pomeranian Medical University, Szczecin, Poland. mzrata01@louisville.edu.
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002630:Chemotactic Factors / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D011422:Propionates / Q000494:pharmacology / Q000627:therapeutic use; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D059016:Tumor Microenvironment / Q000187:drug effects / Q000528:radiation effects; D014750:Vincristine / Q000494:pharmacology
chemical_list: C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; D002630:Chemotactic Factors; D007555:Isoxazoles; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; D014750:Vincristine; C032881:lysophosphatidic acid