Expression of matrix metalloproteinases in human glioma cell lines in the presence of IL-10

Matrix metalloproteinases have been implicated to play a vital role in glio ma invasion as they degrade extracellular matrix to facilitate the subseque nt migration of tumor cells into the surrounding brain tissue. The cytokine Interleukin-10 (IL-10) was detected recently in glial tumors in vivo. Expr ession of specific IL-10 mRNA as well as blood serum levels of IL-10 in gli oma patients increased with malignancy suggesting a functional role of IL-1 0 in glioma progression. Moreover, glioma cell migration in vitro was enhan ced in the presence of IL-10. We therefore investigated the expression of t he matrix metalloproteinases (MMPs) stromelysin-1 (MMP-3), 72-kDa collagena se (MMP-2), 92-kDa collagenase (MMP-9), matrilysin (MMP-7) and the human ma crophage metalloelastase (MMP-12). In addition, a possible relation between exposure of glioma cells to IL-10 and invasiveness of these cells due to M MP expression was analyzed. Experiments with Matrigel coated Boyden chamber s revealed a pronounced dose dependent effect of IL-10 on glioma invasivene ss. The synthetic MMP-inhibitor Marimastat markedly reduced cell invasion i n the Boyden chambers confirming the significance of MMPs in the process of invasion. Subsequently, the expression level of MMPs and the serine protea se uPA was investigated in 7 glioma cell lines (U373, GaMG, U251, GHE, SNB1 9, U138 and D54) by RT-PCR. In all but one cell line no enhancement of MMP expression by IL-10 was detected. Matrilysin in U373 cells was the only pro tease found to be upregulated in the presence of IL-10 dependent on cell de nsity. The present data suggest that IL-10 related effects on the invasive properties of the cell lines are not directly mediated by an upregulation o f matrix metalloproteinase expression.