title: Saturated and mono-unsaturated lysophosphatidylcholine metabolism in tumour cells: a potential therapeutic target for preventing metastases.
abstract: BACKGROUND
  Metastasis is the leading cause of mortality in malignant diseases. Patients with metastasis often show reduced Lysophosphatidylcholine (LysoPC) plasma levels and treatment of metastatic tumour cells with saturated LysoPC species reduced their metastatic potential in vivo in mouse experiments. To provide a first insight into the interplay of tumour cells and LysoPC, the interactions of ten solid epithelial tumour cell lines and six leukaemic cell lines with saturated and mono-unsaturated LysoPC species were explored.
  
  
  METHODS
  LysoPC metabolism by the different tumour cells was investigated by a combination of cell culture assays, GC and MS techniques. Functional consequences of changed membrane properties were followed microscopically by detecting lateral lipid diffusion or cellular migration. Experimental metastasis studies in mice were performed after pretreatment of B16.F10 melanoma cells with LysoPC and FFA, respectively.
  
  
  RESULTS
  In contrast to the leukaemic cells, all solid tumour cells show a very fast extracellular degradation of the LysoPC species to free fatty acids (FFA) and glycerophosphocholine. We provide evidence that the formerly LysoPC bound FFA were rapidly incorporated into the cellular phospholipids, thereby changing the FA-compositions accordingly. A massive increase of the neutral lipid amount was observed, inducing the formation of lipid droplets. Saturated LysoPC and to a lesser extent also mono-unsaturated LysoPC increased the cell membrane rigidity, which is assumed to alter cellular functions involved in metastasis. According to that, saturated and mono-unsaturated LysoPC as well as the respective FFA reduced the metastatic potential of B16.F10 cells in mice. Application of high doses of liposomes mainly consisting of saturated PC was shown to be a suitable way to strongly increase the plasma level of saturated LysoPC in mice.
  
  
  CONCLUSIONS
  These data show that solid tumours display a high activity to hydrolyse LysoPC followed by a very rapid uptake of the resulting FFA; a mechanistic model is provided. In contrast to the physiological mix of LysoPC species, saturated and mono-unsaturated LysoPC alone apparently attenuate the metastatic activity of tumours and the artificial increase of saturated and mono-unsaturated LysoPC in plasma appears as novel therapeutic approach to interfere with metastasis.
authors.affiliation: Department of Lipids & Liposomes, Tumor Biology Center, Clinical Research, Breisacher Str. 117, 79106, Freiburg, Germany. raynor@tumorbio.uni-freiburg.de.
authors.forename: Anna
authors.initials: A
authors.lastname: Raynor
authors.affiliation: ProQinase GmbH, Breisacher Str. 117, 79106, Freiburg, Germany. p.jantscheff@proqinase.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Jantscheff
authors.affiliation: Department of Pharmaceutical Chemistry, University of Bonn, An der Immenburg 4, 53121, Bonn, Germany. tross@uni-bonn.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ross
authors.affiliation: Department of Pharmaceutical Chemistry, University of Bonn, An der Immenburg 4, 53121, Bonn, Germany. martin.schlesinger@uni-bonn.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlesinger
authors.affiliation: Department of Lipids & Liposomes, Tumor Biology Center, Clinical Research, Breisacher Str. 117, 79106, Freiburg, Germany. maurice.wilde@web.de.|Institute for Pharmaceutical Sciences, University of Freiburg, Albertstr. 25, 79104, Freiburg, Germany. maurice.wilde@web.de.
authors.forename: Maurice
authors.initials: M
authors.lastname: Wilde
authors.affiliation: Department of Lipids & Liposomes, Tumor Biology Center, Clinical Research, Breisacher Str. 117, 79106, Freiburg, Germany. sina.haasis@online.de.|Institute for Pharmaceutical Sciences, University of Freiburg, Albertstr. 25, 79104, Freiburg, Germany. sina.haasis@online.de.
authors.forename: Sina
authors.initials: S
authors.lastname: Haasis
authors.affiliation: Department of Lipids & Liposomes, Tumor Biology Center, Clinical Research, Breisacher Str. 117, 79106, Freiburg, Germany. timdreckmann@gmail.com.|Institute for Pharmaceutical Sciences, University of Freiburg, Albertstr. 25, 79104, Freiburg, Germany. timdreckmann@gmail.com.
authors.forename: Tim
authors.initials: T
authors.lastname: Dreckmann
authors.affiliation: Department of Pharmaceutical Chemistry, University of Bonn, An der Immenburg 4, 53121, Bonn, Germany. gbendas@uni-bonn.de.
authors.forename: Gerd
authors.initials: G
authors.lastname: Bendas
authors.affiliation: Department of Lipids & Liposomes, Tumor Biology Center, Clinical Research, Breisacher Str. 117, 79106, Freiburg, Germany. ulrich.massing@pharmazie.uni-freiburg.de.|Institute for Pharmaceutical Sciences, University of Freiburg, Albertstr. 25, 79104, Freiburg, Germany. ulrich.massing@pharmazie.uni-freiburg.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Massing
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D005591:Chemical Fractionation; D005227:Fatty Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000097:blood / Q000378:metabolism*; D008297:Male; D008560:Membrane Fluidity; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009369:Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology
chemical_list: D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D008244:Lysophosphatidylcholines