Structural changes in the extracellular matrix (ECM) are necessary for cell migration during tissue remodeling and local neoplastic cell invasion. The
matrix metalloproteinases (
MMPs) and their inhibitors have been shown to be critical modulators of ECM composition and are thus, crucial in
tumor cell invasion and
metastasis. The immunocytochemical profile of MMP-2, -3, -9, -10, and -13 expression was observed in 24 primary human childhood
astrocytomas (ASTRs) employing an indirect
alkaline phosphatase conjugated
antigen detection technique. Evaluation of the results was based on (a) the percent of neoplastically transformed cells that reacted positively and (b) a measure of staining intensity [graded from A (highest) to D (negative)]. The two forms of
stromelysin, MMP-3 and -10, share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by
cytokines and
growth factors in vitro. Strong overall expression of MMP-3 and -10 was found in ASTRs, especially in the ECM adjacent to blood vessels. Positive immunoreactivity could be seen for these two
MMPs in the ECM surrounding over 90% of the neoplastically transformed cells (+4) and the staining intensity was also the strongest possible (A,B). No immunoreactivity was detected using
antibodies directed against MMP-2, -9, and -13. Based on these results, MMP-3 and -10 are implicated in the pathogenesis of pediatric ASTRs. Further characterization of the expression and utilization of
MMPs and their inhibitors in the progression of ASTRs may establish differential regulation and utilization of the various
MMPs during the progression of glial
tumors, from low-grade pilocytic ASTR to high-grade
glioblastoma multiforme.