Matrix metalloproteinase (
MMP) expression and production are associated with advanced-stage
tumor and contribute to
tumor progression, invasion and
metastases. The current study was designed to determine the expression and production of MMP-2 (
gelatinase A) and MMP-9 (
gelatinase B) by human lymphoid
tumor cells. Changes in expression and production were also investigated during
tumor progression of
multiple myeloma and
mycosis fungoides. In situ hybridization analysis revealed that
lymphoblastic leukemia B cells (SB cell line),
multiple myeloma (MM) cells (U266 cell line) and
lymphoblastic leukemia T cells (CEM and Jurkat cell lines) express constitutively the
mRNA for MMP-2 and/or MMP-9. We demonstrated by
gelatin-zymography of cell culture medium that both
enzymes were secreted in their cleaved (activated) form. In situ hybridization of bone marrow plasma cells and
gelatin-zymography of the medium showed that patients with active MM (diagnosis, relapse, leukemic progression) express higher levels of MMP-2
mRNA and
protein than patients with non-active MM (complete/objective response, plateau) and with
monoclonal gammopathies of undetermined significance (MGUS). MMP-9 expression and secretion was similar in all patient groups. In patients with
mycosis fungoides (MF), the expression of MMP-2 and MMP-9 mRNAs was significantly upregulated with advancing stage, in terms of lesions both positive for one of two mRNAs and with the greatest intensity of expression. Besides MF cells, the MMP-2 and/or MMP-9 mRNAs were expressed by some stromal cell populations (microvascular endothelial cells, fibroblasts, macrophages), suggesting that these cells cooperate in the process of
tumor invasion. Our studies identify
MMPs as an important class of
proteinases involved in the extracellular matrix (ECM) degradation by human lymphoid
tumors, and suggest that
MMPs inhibitors may lead to important new treatment for their control.