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 expressed in malignant glioma cells and that this increased expression may facilitate the invasiveness of tumor cells. The authors investigated the expression and enzymatic activity of MMPs in rat brain during the growth of malignant gliomas at different time intervals. C6 rat glioma cells were unilaterally implanted into rat cerebral hemispheres. After 7 or 14 days, these brain tissues were prepared for SDS-PAGE zymography, Western blotting, immunohistochemistry, and in situ zymography. SDS-PAGE zymography and Western blotting revealed that the expression of proMMP-2 in rat brains with C6 glioma cells 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 former but not in the latter. On immunohistochemistry, C6 glioma cells presenting invasive growth into the rat brain parenchyma and vessels demonstrated MMP-2 immunoreactivity. On in situ zymography, foci of invasive C6 glioma cells in rat brain tissue showed gelatinolytic activity. These results suggest that expression and activation of MMP-2 may be one of the crucial steps for glioma cell invasion into the brain parenchyma in vivo.