Matrix metalloproteinase (MMP)-3 (stromelysin-1) degrades various components of the extracellular matrix as well as several non-matrix components; it has notably been shown to activate other MMPs relevant to cancer and metastasis, including MMP-9. MMP-3 gene expression in the tumor microenvironment could therefore contribute to cancer progression. Transcriptional regulation of MMP genes was often described to occur upon intercellular interactions, leading to overexpression of these genes by cancer and/or stromal cells. In the present Work, we report that expression of MMP-3 in T lymphoma cells is transiently induced during specific intercellular contact with endothelial cells (EC). Moreover, mice injected with lymphoma cells expressing MMP-3 constitutively developed thymic lymphoma more rapidly than those injected with control lymphoma cells. We also found that overexpression. of MMP-3 in lymphoma transfectants significantly improved their ability to migrate through the matrix when compared to cells transfected with the control vector. These results provide the first in vivo evidence that local expression of MMP-3 promotes lymphoma progression and indicate that MMP-3 expression is tightly regulated upon lymphoma cell/stromal cell interaction. (C) 2004 Elsevier Inc. All rights reserved.