title: CD26 expression on T cell lines increases SDF-1-alpha-mediated invasion.
abstract: BACKGROUND
  CD26 is a multifunctional membrane-bound glycoprotein that regulates tumour growth in addition to its other activities. Because disease aggressiveness is correlated with CD26 expression in several T-cell malignancies, we decided to investigate the invasiveness of cells expressing different levels of CD26.
  
  
  METHODS
  To assess CD26 involvement in cell invasion, we performed in vitro invasion assays with human T cell lines expressing different levels of CD26. These included the parental CD26-positive T-lymphoblast cell line HSB-2 and clones infected with a retrovirus expressing siRNA vectors that either targeted CD26 or encoded a missense siRNA, and the parental CD26-negative T-leukaemia cell line Jurkat and clones expressing CD26. CD26 expression in these cell lines was evaluated by flow cytometry and western immunoblotting. CXCR4 expression, phosphorylation of signalling kinases, and MMP-9 secretion were also evaluated by western immunoblotting, whereas MMP-9 activity and the effect of kinase and CD45 inhibitors on activity were measured by zymography of conditioned media.
  
  
  RESULTS
  The presence of CD26 enhanced stromal-cell-derived factor-1-alpha (SDF-1-alpha)-mediated invasion of T cell lines. This process was regulated in part by the PI-3K and MEK1 pathways, as indicated by increased phosphorylation of p44/42 MAP kinase and Akt in the presence of SDF-1-alpha and the effect of their respective inhibitors on MMP-9 secretion and in vitro invasion. In addition, CD26-associated enhancement of SDF-1-alpha-induced invasion was decreased when CD45 was inhibited.
  
  
  CONCLUSIONS
  Our results indicate that the expression of CD26 in T cell lines leads to increased SDF-1-alpha-mediated invasion in an in vitro system and that this is controlled in part by the PI-3K and MEK1 pathways. The data also suggest that CD26 enhancement of invasion may be mediated by CD45, however, more studies are required to confirm this involvement.
authors: Division of Hematology/Oncology, University of Florida, Gainesville, FL 32610, USA.
authors: P A
authors: PA
authors: Havre
authors: M
authors: M
authors: Abe
authors: Y
authors: Y
authors: Urasaki
authors: K
authors: K
authors: Ohnuma
authors: C
authors: C
authors: Morimoto
authors: N H
authors: NH
authors: Dang
mesh_terms: D054377:Chemokine CXCL12 / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000037:antagonists & inhibitors; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009025:Morpholines / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000032:analysis; D014162:Transfection
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D002867:Chromones; D009025:Morpholines; D047428:Protein Kinase Inhibitors; D019718:Receptors, CXCR4; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D048049:Extracellular Signal-Regulated MAP Kinases; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D020780:Matrix Metalloproteinase 9