The expression and activation of matrix metalloproteinase-2 in rat brain after implantation of C6 rat glioma cells

It has been reported that matrix metalloproteinases (MMPs) are highly expre ssed in malignant glioma cells and that this increased expression may facil itate the invasiveness of tumor cells. The authors investigated the express ion and enzymatic activity of MMPs in rat brain during the growth of malign ant gliomas at different time intervals. C6 rat glioma cells were unilatera lly implanted into rat cerebral hemispheres. After 7 or 14 days, these brai n tissues were prepared for SDS-PAGE zymography, Western blotting, immunohi stochemistry, and in situ zymography. SDS-PAGE zymography and Western blott ing revealed that the expression of proMMP-2 in rat brains with C6 glioma c ells was significantly higher than that in normal or the sham-operated rat brains, and that the activated form of MMP-2 was detected only in the forme r but not in the latter. On immunohistochemistry, C6 glioma cells presentin g invasive growth into the rat brain parenchyma and vessels demonstrated MM P-2 immunoreactivity. On in situ zymography, foci of invasive C6 glioma cel ls in rat brain tissue showed gelatinolytic activity. These results suggest that expression and activation of MMP-2 may be one of the crucial steps fo r glioma cell invasion into the brain parenchyma in vivo.