EXPRESSION OF TISSUE INHIBITORS OF METALLOPROTEINASES - NEGATIVE REGULATORS OF HUMAN GLIOBLASTOMA INVASION IN-VIVO

Tissue inhibitors of metalloproteinases (TIMPs) are negative regulator s of matrix metalloproteinases (MMPs) which degrade major components o f the extracellular matrix, The aberrant expression of TIMPs is believ ed to represent an important modulating factor in the invasive capacit y of human tumors, In the present study we analyzed the expression of TIMPs in human brain tumor tissue samples by an enzyme-linked immunoso rbent assay (ELISA) and by Northern blotting analysis, Quantitation of TIMP-1 and TIMP-2 by ELISA demonstrated low levels of TIMP-1 and TIMP -2 proteins in glioblastomas, and moderate levels in anaplastic astroc ytomas compared with normal brain tissues low-grade gliomas and metast atic tumors (renal and breast carcinomas and melanomas), Northern blot analysis of TIMP-1 transcripts demonstrated higher expression in meni ngioma, normal brain tissues and other metastatic tumors than in anapl astic astrocytoma and glioblastoma, Two distinct transcripts of 1.0 an d 3.5 kb were observed for TIMP-2 mRNA in normal brain tissue and in t umor extracts, In addition, TIMP-2 mRNA expression was lower in gliobl astoma and anaplastic astrocytoma than in meningioma, normal brain tis sues and metastatic tumors, These findings suggest that down-regulatio n of both TIMP-1 and TIMP-2 contributes significantly to the invasive potential of human glioblastoma multiforme and anaplastic astrocytomas .