We observed that sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) strongly
enhance in vitro motility and adhesion of human rhabdomyosarcoma (RMS) cells. This effect was
observed at physiological concentrations of both bioactive lipids, which are present in biological
fluids, and is much stronger than the effects observed in response to known RMS pro-metastatic
factors such as stromal derived factors-1 (SDF-1) or hepatocyte growth factor/scatter factor
(HGF/SF). We also present novel evidence that the levels of S1P and C1P increase in several organs
after γ-irradiation or chemotherapy, which indicates induction of an unwanted pro-metastatic
environment related to treatment. Most importantly, 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. We propose that bioactive lipids play a previously
underappreciated role in dissemination of RMS and the unwanted side effects of radio/chemotherapy by
creating a pro-metastatic microenvironment. Therefore, an anti-metastatic treatment with specific
S1P-binding scavenger such as NOX-S93 could become a part of standard radio/chemotherapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.