title: CXCR4 and matrix metalloproteinase-2 are involved in mesenchymal stromal cell homing and engraftment to tumors.
abstract: OBJECTIVE
  Bone marrow-derived mesenchymal stromal cells (BMSC) have been shown to migrate to injury, ischemia and tumor microenvironments. The mechanisms by which mesenchymal stromal cells (MSC) migrate across endothelium and home to the target tissues are not yet fully understood.
  
  
  METHODS
  We used rat BMSC to investigate the molecular mechanisms involved in their tropism to tumors in vitro and in vivo.
  
  
  RESULTS
  BMSC were shown to migrate toward four different tumor cells in vitro, and home to both subcutaneous and lung metastatic prostate tumor models in vivo. Gene expression profiles of MSC exposed to conditioned medium (CM) of various tumor cells were compared and revealed that matrix metalloproteinase-2 (MMP-2) expression in BMSC was downregulated after 24 h exposure to tumor CM. Chemokine (C-X-C motif) Receptor 4 (CXCR4) upregulation was also found in BMSC after 24 h exposure to tumor CM. Exposure to tumor cell CM enhanced migration of BMSC toward tumor cells. Stromal Cell-Derived Factor (SDF-1) inhibitor AMD3100 and MMP-2 inhibitor partly abolished the BMSC migration toward tumor cells in vitro.
  
  
  CONCLUSIONS
  These results suggest that the CXCR4 and MMP-2 are involved in the multistep migration processes of BMSC tropism to tumors.
authors.affiliation: Stem Cell and Regeneration Program, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Song
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D001596:Benzylamines; D045744:Cell Line, Tumor; D002465:Cell Movement; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000080027:Cyclams; D020869:Gene Expression Profiling; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000235:genetics / Q000502:physiology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
chemical_list: D001596:Benzylamines; D017077:Culture Media, Conditioned; C486264:Cxcr4 protein, rat; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D020778:Matrix Metalloproteinase 2; C088327:plerixafor