Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.11 (
CD10
)
9,792
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Tissue inhibitor of metalloproteinase 1
(
TIMP-1
) is a stromal factor with multiple functions. Overexpression of
TIMP-1
correlates with aggressive clinical behavior of a spectrum of tumors. Here, for the first time, we address the role of
TIMP-1
in the pathogenesis of B-cell lymphomas. An Epstein-Barr virus (EBV)-negative Burkitt lymphoma cell line with ectopic
TIMP-1
expression (TIMP-1JD38) was used to identify genes induced/repressed by
TIMP-1
. Differentially expressed genes were analyzed by cDNA microarray, and they were validated by immunohistochemistry, flow cytometry, and Western blotting. Analysis revealed changes of genes coding for B-cell growth/differentiation, transcription, and cell cycle regulators.
TIMP-1
repressed expression of germinal center (GC) markers
CD10
, Bcl-6, PAX-5 and up-regulated plasma cell-associated antigens CD138, MUM-1/IRF-4, XBP-1, and CD44, suggesting a plasma cell differentiation. This is accompanied by activation of signal transducer and activator of transcription 3 (STAT-3) and switch to cyclin D2 expression. However, TIMP-1JD38 cells expressed an inactive form of XBP-1, lacking antibody production/secretion. This incomplete plasmacytic differentiation occurs without altering cell proliferation, and despite c-Myc deregulation, indicating an arrested plasmacytic/plasmablastic stage of differentiation. Further validation in human lymphoma cell lines and in primary B-cell tumors demonstrated a predominant
TIMP-1
expression in tumors with plasmacytic/plasmablastic phenotypes, including multiple myelomas. These findings strongly support
TIMP-1
as an important factor in the pathogenesis of plasmacytic/plasmablastic tumors.
...
PMID:Tissue inhibitor of metalloproteinase 1 (TIMP-1) promotes plasmablastic differentiation of a Burkitt lymphoma cell line: implications in the pathogenesis of plasmacytic/plasmablastic tumors. 1547 29
