Expression of matrix metalloproteinases and their inhibitors in human brain tumors

Sixty human brain tumors, classified according to the New World Health Orga nization (WHO) classification including, grade I schwannomas, meningiomas a nd pilocytic astrocytomas, grade II astrocytomas, grade III anaplastic astr ocytomas, grade IV glioblastomas, grade III anaplastic oligodendrogliomas a nd grade IV glioblastomas and lung and melanoma metastases were analyzed fo r the expression of three matrix metalloproteinases (MMPs), two tissue inhi bitors of MMPs (TIMPs) and for MMP activity. Some correlation was found bet ween MMP expression and the degree of malignancy. Western blotting analysis revealed a more uniform pattern of distribution of MMP-2 (gelatinase A) th an of MMP-9 (gelatinase B) and MMP-12 (metalloelastase) among tumors. MMP-9 levels were found to be significantly higher in grade III anaplastic astro cytomas and anaplastic oligodendrogliomas than those in grade I schwannomas and meningiomas. Anaplastic astrocytomas and Grade IV glioblastomas expres sed significantly higher levels MMP-12 than grade I meningiomas. All sixty tumors showed a similar pattern of activity in zymography, proMMP-9 being t he major species detected. Interestingly, TIMP-1 and TIMP-2 expression leve ls were especially low in tumors of grade II and grade III but significantl y higher in tumors of grade I, particularly in schwannomas. Taken together, these data suggest that: 1) a balance between MMPs and TIMPs has an import ant role to play in human brain tumors; 2) TIMP expression may be valuable markers for tumor malignancy.