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
1 Division of Hematology/Oncology, University of Florida Shands Cancer Center, Gainesville, FL 32610, USA
2 Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan
3 Division of Hematology/Oncology, University of Florida, 1600 SW Archer Road, Box 100278, Gainesville, Florida 32610, USA
BMC Cancer 2013, 13:517 doi:10.1186/1471-2407-13-517Published: 1 November 2013
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.
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.
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.
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.