Expression of the matrix metalloproteinase 9 in Hodgkin's disease is independent of EBV status.
BACKGROUND
In vitro the Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP-1) has been shown to upregulate expression of matrix metalloproteinase 9 (MMP-9), a member of a family of zinc dependent endopeptidases that is believed to facilitate tumour invasion and metastasis by degradation of the extracellular matrix.


OBJECTIVE
To test whether the expression of MMP-9 in Hodgkin's disease correlates with EBV status and survival and to investigate whether LMP-1 expression affects MMP-9 concentrations in the Hodgkin's disease cell line, L428.


METHODS
MMP-9 expression was measured by means of immunohistochemistry in a series of Hodgkin's disease tumours and this expression was correlated with EBV status and survival. The influence of LMP-1 on MMP-9 expression was also investigated in the Hodgkin's disease cell line, L428.


RESULTS
MMP-9 expression was demonstrated in the malignant Hodgkin and Reed-Sternberg cells of all (n = 86) formalin fixed, paraffin wax embedded Hodgkin's disease tumours examined. Although the intensity of MMP-9 immunostaining varied between cases, there was no correlation between MMP-9 expression and EBV status or survival. MMP-9 expression was also detected in a variety of non-malignant cells, including fibroblasts. MMP-9 was detected by zymography in the L428 and KMH2 Hodgkin's disease cell lines, whereas low or undetectable amounts of MMP-9 were found in the L591 Hodgkin's disease cell line. Induction of LMP-1 expression in the Hodgkin's disease cell line L428 did not result in a detectable increase in the values of MMP-9 as measured by zymography.


CONCLUSIONS
These results demonstrate that MMP-9 is consistently expressed by the Hodgkin and Reed-Sternberg cells of Hodgkin's disease tumours and by the Hodgkin's disease cell lines, L428 and KMH2. However, this expression does not appear to be related either to LMP-1 values or to survival.
Flavell
J R
JR
Biomedical Science Research Laboratories, School of Health Sciences, University of Wolverhampton, UK.
Baumforth
K R
KR
Williams
D M
DM
Lukesova
M
M
Madarova
J
J
Noskova
V
V
Prochazkova
J
J
Lowe
D
D
Kolar
Z
Z
Murray
P G
PG
Nelson
P N
PN
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006689:Hodgkin Disease / Q000201:enzymology* / Q000821:virology; D006801:Humans; D007124:Immunoenzyme Techniques; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000378:metabolism
D014408:Biomarkers, Tumor; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D020780:Matrix Metalloproteinase 9