title: The role of sphingosine-1 phosphate and ceramide-1 phosphate in trafficking of normal stem cells and cancer cells.
abstract: BACKGROUND
  A common feature of many types of cells is their responsiveness to chemotactic gradients of factors for which they express the corresponding receptors. The most studied chemoattractants so far are peptide-based growth factors and a family of cytokines endowed with strong chemotactic properties, called chemokines. However, additional evidence has accumulated that, in addition to these peptide-based chemoattractants, an important role in cell migration is played by bioactive lipids.
  
  
  METHODS
  Solid evidence has accumulated that two bioactive phosphorylated sphingolipids that are derivatives of sphingolipid metabolism, namely sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), are potent chemoattractants for a variety of cells. In this review, we will discuss the effect of these two phosphorylated sphingolipids on the trafficking of normal and malignant cells, and, in particular, we will focus on their role in trafficking of normal hematopoietic stem/progenitor cells. Unlike other mediators, S1P under steady-state conditions maintain a steep gradient between interstitial fluid and peripheral blood and lymph across the endothelial barrier, which is important in the egress of cells from bone marrow. Both S1P and C1P may be upregulated in damaged tissues, which may result in reversal of this gradient.
  
  
  CONCLUSIONS
  S1P and C1P are important regulators of the trafficking of normal and malignant cells, and modification of their biological effects will have important applications in optimizing stem cell mobilization and homing, tissue organ/regeneration, and preventing cancer metastasis.
authors.affiliation: University of Louisville, Stem Cell Institute, James Graham Brown Cancer Center , 500 S. Floyd Street, Rm. 107, Louisville, KY 40202 , USA +1 502 852 1788 ; +1 502 852 3032 ; mzrata01@louisville.edu.
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
authors.forename: Malwina
authors.initials: M
authors.lastname: Suszynska
authors.forename: Sylwia
authors.initials: S
authors.lastname: Borkowska
authors.forename: Janina
authors.initials: J
authors.lastname: Ratajczak
authors.forename: Gabriela
authors.initials: G
authors.lastname: Schneider
mesh_terms: D001692:Biological Transport; D002518:Ceramides / Q000502:physiology*; D006801:Humans; D008246:Lysophospholipids / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D002518:Ceramides; D008246:Lysophospholipids; C065576:ceramide 1-phosphate; C060506:sphingosine 1-phosphate; D013110:Sphingosine