title: The involvement of stromal derived factor 1alpha in homing and progression of multiple myeloma in the 5TMM model.
abstract: OBJECTIVE
  Multiple myeloma (MM) is a lethal plasma cell cancer characterized by the monoclonal growth of cells in the bone marrow. To reach the bone marrow, MM cells need to be attracted by chemokines. Recently, it has been shown that chemokines can also be involved in the growth of several cancer types. Stromal cell derived factor 1a (SDF1alpha) or CXCL12 is known to play an important role as a chemokine for hematopoietic progenitor cells and human MM cells. We studied the effects of SDF1a in the 5TMM murine model.
  
  
  METHODS
  The in vitro effects of SDF1alpha were analyzed by gelatin zymography, adhesion, migration, proliferation, and chemoinvasion assays and by blockade with the CXCR4 inhibitor, 4F-benzoyl-TN14003. In vivo, diseased mice were treated with either vehicle or 4F-benzoyl-TN14003.
  
  
  RESULTS
  In vitro SDF1alpha was capable of attracting both 5T2MM and 5T33MM cells and inducing a 1.6-fold increase in MMP9 production by the 5TMM cells, which was correlated with an increased invasive capacity. In addition, SDF1alpha induced a 20% increase in DNA synthesis in the 5TMM cells. All these effects could be blocked by the CXCR4 inhibitor, 4Fbenzoyl- TN14003. An in vivo study in the 5T33MM model showed that blocking CXCR4 led to a 20% reduction in bone marrow tumor load.
  
  
  CONCLUSIONS
  These data demonstrate that SDF1alpha/CXCR4 is involved in the homing and the expansion of MM cells. Blocking CXCR4 could be useful in synergy with other anti-neoplastic treatments targeting the bone marrow microenvironment.
authors.affiliation: Department of Hematology and Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Eline
authors.initials: E
authors.lastname: Menu
authors.forename: Kewal
authors.initials: K
authors.lastname: Asosingh
authors.forename: Stefano
authors.initials: S
authors.lastname: Indraccolo
authors.forename: Hendrik
authors.initials: H
authors.lastname: De Raeve
authors.forename: Ivan
authors.initials: I
authors.lastname: Van Riet
authors.forename: Els
authors.initials: E
authors.lastname: Van Valckenborgh
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vande Broek
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van de Broek
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tamamura
authors.forename: Ben
authors.initials: B
authors.lastname: Van Camp
authors.forename: Karin
authors.initials: K
authors.lastname: Vanderkerken
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002461:Cell Line, Transformed / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: C477728:4-fluorobenzoyl-TN-14003; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D009363:Neoplasm Proteins; D010455:Peptides; D019718:Receptors, CXCR4; D020780:Matrix Metalloproteinase 9