Stromelysin-2 (Matrix Metalloproteinase 10) Is Inducible in Lymphoma Cells and Accelerates the Growth of Lymphoid Tumors In Vivo

Abstract

Matrix metalloproteinase (MMP) 10 (stromelysin-2) is known to degrade various components of the extracellular matrix; however, the signals that regulate its expression and its role in lymphoma growth remain unknown. In the present work, we report the up-regulated expression of MMP10 in T lymphoma cells following contact with endothelial cells. The induction of MMP10 was found to be dependent on the specific interaction between LFA-1 and ICAM-1, which play a central role in regulating the expression of genes involved in the rate-limiting steps of lymphoma development. MMP10, but not MMP3 (stromelysin-1), was also up-regulated in human B lymphoma cells following exposure to IL-4, IL-6, and IL-13, but not to IL-1. To gain further insight into the role of MMP10 in lymphoma development, we generated lymphoma cell lines constitutively expressing high levels of MMP10 and studied these cells for their ability to form thymic lymphoma in vivo. Mice injected with lymphoma cells constitutively expressing MMP10 developed thymic lymphoma more rapidly than those injected with control lymphoma cells. These results provide the first in vivo evidence that overexpression of MMP10 promotes tumor development, and indicate that MMP10 induction is an important pathway activated not only upon ICAM-1/LFA-1-mediated intercellular contact, but also following activation of tumor cells with inflammatory cytokines.

Matrix metalloproteinase-10 is a critical effector of protein kinase Cι-Par6α-mediated lung cancer

“…Overexpression of exogenous MMP-10 in mouse T-cell lymphoma cells leads to more rapidly growing tumors in nude mice than control cells, suggesting a role for MMP-10 in lymphoma cell growth (Van Themsche et al, 2004). However, the question of whether endogenous MMP-10 was required for tumor growth was not assessed in this study.…”

Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues

“…Other studies have observed MMP10 upregulation in oesophageal carcinomas (Mathew et al, 2002), recurrent lung carcinomas (Cho et al, 2004) and in gliomas (Thorns et al, 2003), where they predict a more malignant phenotype. Similarly, Van Themsche et al (2004) found that induction of MMP10 expression in lymphoma cell lines promoted their malignant phenotype.…”

Identification of Novel Targets of MYC Whose Transcription Requires the Essential MbII Domain

“…Induction of the metalloprotease MMP10 in MYC expressing tumors may help facilitate basement membrane digestion by invasive tumor cells and/or other processes critical for malignancy. 52 For several of these targets, we have proceeded to further characterize their regulation by MYC using chromatin immunoprecipitation to map the MYC binding site(s) and depleting cellular MYC with shRNA to confirm that endogenous MYC controls their transcription. We have recently reported, for example, that the gene for the metastasis regulator MTA1 contains several high affinity MYC binding sites and that depletion of endogenous MYC causes a selective decrease in MTA1 transcript levels in a variety of cell lines.…”