MMP-7 (matrilysin) expression in human brain tumors

Matrix metalloproteinases (MMP) which degrades protein components of the extra-cellular matrix and basement membrane seems to be largely involved in cancer invasiveness. MMP proteolitic activity essentially comes from stromal cells but matrilysin (MMP-7) is produced by the tumor itself. Thus, MMP-7 is investigated to address the particular invasive behavior of human glioma. Both MMP-7 mRNA and protein were clearly identified in human glioma. MMP-7 mRNA expression was highly variable within our glioma population. When analyzing MMP-7 mRNA expression in different primary brain tumors, we found highly variable levels of expression not related to their invasive behavior. In successive biopsies obtained in the same patients with glioblastoma, MMP-7 mRNA was quantified and appeared variable, but intra-individual variations were lower than inter-individual differences. With a xenograft model of U87 human tumors in RAG2/gamma(c) immune-deficient mice, the strict tumor origin of MMP-7 was shown. Additionally, MMP-7 expression by U87 cells which is low in culture was stimulated by these cells while forming tumors and the level of expression was higher when the tumor cells were implanted within the brain. These data provide some consistent information about cross-talk occurring between the tumor and the surrounding stroma to regulate MMP-7 expression.