PMID- 23615526
OWN - NLM
STAT- MEDLINE
DCOM- 20140421
LR  - 20211021
IS  - 1557-3125 (Electronic)
IS  - 1541-7786 (Print)
IS  - 1541-7786 (Linking)
VI  - 11
IP  - 7
DP  - 2013 Jul
TI  - Bioactive lipids S1P and C1P are prometastatic factors in human rhabdomyosarcoma, 
      and their tissue levels increase in response to radio/chemotherapy.
PG  - 793-807
LID - 10.1158/1541-7786.MCR-12-0600 [doi]
AB  - 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 gamma-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.
CI  - (c)2013 AACR
FAU - Schneider, Gabriela
AU  - Schneider G
AD  - Stem Cell Institute at James Graham Brown Cancer Center, University of 
      Louisville, 500 S. Floyd Street, Louisville, KY 40202, USA.
FAU - Bryndza, Ewa
AU  - Bryndza E
FAU - Abdel-Latif, Ahmed
AU  - Abdel-Latif A
FAU - Ratajczak, Janina
AU  - Ratajczak J
FAU - Maj, Magdalena
AU  - Maj M
FAU - Tarnowski, Maciej
AU  - Tarnowski M
FAU - Klyachkin, Yuri M
AU  - Klyachkin YM
FAU - Houghton, Peter
AU  - Houghton P
FAU - Morris, Andrew J
AU  - Morris AJ
FAU - Vater, Axel
AU  - Vater A
FAU - Klussmann, Sven
AU  - Klussmann S
FAU - Kucia, Magdalena
AU  - Kucia M
FAU - Ratajczak, Mariusz Z
AU  - Ratajczak MZ
LA  - eng
GR  - R01 DK074720/DK/NIDDK NIH HHS/United States
GR  - R01 HL112788/HL/NHLBI NIH HHS/United States
GR  - S10 RR024598/RR/NCRR NIH HHS/United States
GR  - 2R01 DK074720/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130424
PL  - United States
TA  - Mol Cancer Res
JT  - Molecular cancer research : MCR
JID - 101150042
RN  - 0 (Actins)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Aptamers, Nucleotide)
RN  - 0 (Ceramides)
RN  - 0 (Lysophospholipids)
RN  - 0 (Receptors, Lysosphingolipid)
RN  - 0 (ceramide 1-phosphate)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Aptamers, Nucleotide/pharmacology
MH  - Bone Marrow/drug effects/radiation effects
MH  - Cell Adhesion/drug effects/radiation effects
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects/radiation effects
MH  - Cell Proliferation/drug effects/radiation effects
MH  - Cell Survival/drug effects/radiation effects
MH  - Cellular Microenvironment/drug effects/radiation effects
MH  - Ceramides/*metabolism
MH  - Cytoskeleton/drug effects/metabolism
MH  - Down-Regulation/drug effects/radiation effects
MH  - Enzyme Activation/drug effects/radiation effects
MH  - Humans
MH  - Lysophospholipids/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Neoplasm Metastasis
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptors, Lysosphingolipid/metabolism
MH  - Rhabdomyosarcoma/*drug therapy/enzymology/pathology/*radiotherapy
MH  - Sphingosine/*analogs & derivatives/metabolism
PMC - PMC3720846
MID - NIHMS472483
COIS- Conflict of Interest: Gabriela Schneider and Mariusz Ratajczak received minor 
      commercial research funding from NOXXON Pharma AG for studying the effect of 
      NOX-S93 in chemo-radiation induced metastasis of RMS.
EDAT- 2013/04/26 06:00
MHDA- 2014/04/22 06:00
PMCR- 2014/07/01
CRDT- 2013/04/26 06:00
PHST- 2013/04/26 06:00 [entrez]
PHST- 2013/04/26 06:00 [pubmed]
PHST- 2014/04/22 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - 1541-7786.MCR-12-0600 [pii]
AID - 10.1158/1541-7786.MCR-12-0600 [doi]
PST - ppublish
SO  - Mol Cancer Res. 2013 Jul;11(7):793-807. doi: 10.1158/1541-7786.MCR-12-0600. Epub 
      2013 Apr 24.