title: CD26 expression on T-anaplastic large cell lymphoma (ALCL) line Karpas 299 is associated with increased expression of versican and MT1-MMP and enhanced adhesion.
abstract: BACKGROUND
  CD26/dipeptidyl peptidase IV (DPPIV) is a multifunctional membrane protein with a key role in T-cell biology and also serves as a marker of aggressive cancers, including T-cell malignancies.
  
  
  METHODS
  Versican expression was measured by real-time RT-PCR and Western blots. Gene silencing of versican in parental Karpas 299 cells was performed using transduction-ready viral particles. The effect of versican depletion on surface expression of MT1-MMP was monitored by flow cytometry and surface biotinylation. CD44 secretion/cleavage and ERK (1/2) activation was followed by Western blotting. Collagenase I activity was measured by a live cell assay and in vesicles using a liquid-phase assay. Adhesion to collagen I was quantified by an MTS assay.
  
  
  RESULTS
  Versican expression was down-regulated in CD26-depleted Karpas 299 cells compared to the parental T-ALCL Karpas 299 cells. Knock down of versican in the parental Karpas 299 cells led to decreased MT1-MMP surface expression as well as decreased CD44 expression and secretion of the cleaved form of CD44. Parental Karpas 299 cells also exhibited higher collagenase I activity and greater adhesion to collagenase I than CD26-knockdown or versican-knockdown cells. ERK activation was also highest in parental Karpas 299 cells compared to CD26-knockdown or versican-knockdown clones.
  
  
  CONCLUSIONS
  Our data indicate that CD26 has a key role in cell adhesion and invasion, and potentially in tumorigenesis of T-cell lines, through its association with molecules and signal transduction pathways integral to these processes.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Havre
authors.forename: Long H
authors.initials: LH
authors.lastname: Dang
authors.forename: Kei
authors.initials: K
authors.lastname: Ohnuma
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iwata
authors.forename: Chikao
authors.initials: C
authors.lastname: Morimoto
authors.affiliation: Division of Hematology/Oncology, University of Florida Shands Cancer Center, Gainesville, FL 32610, USA. nam.dang@medicine.ufl.edu.
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics* / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000235:genetics* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D015398:Signal Transduction; D053675:Versicans / Q000235:genetics* / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D018960:Hyaluronan Receptors; D053675:Versicans; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D018819:Dipeptidyl Peptidase 4; D017364:Collagenases; C417249:collagenase 1; D053511:Matrix Metalloproteinase 14