Bioactive lipids S1P and C1P are prometastatic factors in human rhabdomyosarcoma, and their tissue levels increase in response to radio/chemotherapy

Gabriela Schneider, Ewa Bryndza, Ahmed Abdel-Latif, Janina Ratajczak, Magdalena Maj, Maciej Tarnowski, Yuri M. Klyachkin, Peter Houghton, Andrew J. Morris, Axel Vater, Sven Klussmann, Magdalena Kucia, Mariusz Z. Ratajczak

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Evidence suggests that bioactive lipids may regulate pathophysiologic functions such as cancer cell metastasis. Therefore, we determined that the bioactive lipid chemoattractants sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) strongly enhanced the in vitro motility and adhesion of human rhabdomyosarcoma (RMS) cells. Importantly, this effect was observed at physiologic concentrations for both bioactive lipids, which are present in biologic fluids, and were much stronger than the effects observed in response to known RMS prometastatic factors such as stromal derived factors-1 (SDF-1/CXCL12) or hepatocyte growth factor/scatter factor (HGF/SF). We also present novel evidence that the levels of S1P and C1P were increased in several organs after γ-irradiation or chemotherapy, which indicates an unwanted prometastatic environment related to treatment. Critically, we found that the metastasis of RMS cells in response to S1P can be effectively inhibited in vivo with the S1P-specific binder NOX-S93 that is based on a high-affinity Spiegelmer. These data indicate that bioactive lipids play a vital role in dissemination of RMS and contribute to the unwanted side effects of radio/chemotherapy by creating a prometastatic microenvironment.

Original languageEnglish (US)
Pages (from-to)793-807
Number of pages15
JournalMolecular Cancer Research
Volume11
Issue number7
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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    Schneider, G., Bryndza, E., Abdel-Latif, A., Ratajczak, J., Maj, M., Tarnowski, M., Klyachkin, Y. M., Houghton, P., Morris, A. J., Vater, A., Klussmann, S., Kucia, M., & Ratajczak, M. Z. (2013). Bioactive lipids S1P and C1P are prometastatic factors in human rhabdomyosarcoma, and their tissue levels increase in response to radio/chemotherapy. Molecular Cancer Research, 11(7), 793-807. https://doi.org/10.1158/1541-7786.MCR-12-0600