Matrix metalloproteinase expression in childhood astrocytomas

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 b e critical modulators of ECM composition and are thus, crucial in tumor cel l invasion and metastasis. The immunocytochemical profile of MMP-2, -3, -9, -10, and -13 expression was observed in 24 primary human childhood astrocy tomas (ASTRs) employing an indirect alkaline phosphatase conjugated antigen detection technique. Evaluation of the results was based on (a) the percen t of neoplastically transformed cells that reacted positively and (b) a mea sure of staining intensity [graded from A (highest) to D (negative)]. The t wo forms of stromelysin, MMP-3 and -10, shale 82% sequence homology, but ex hibit differences in cellular synthesis and inducibility by cytokines and g rowth factors in vitro. Strong over all expression of MMP-3 and -10 was fou nd in ASTRs, especially in the ECM adjacent to blood vessels. Positive immu noreactivity could be seen for these two MMPs in the ECM surrounding over 9 0% of the neoplastically transformed cells (++++) and the staining intensit y was also the strongest possible (A,B). No immunoreactivity was detected u sing antibodies directed against MMP-2, -9, and -13. Based on these results , MMP-3 and -10 are implicated in the pathogenesis of pediatric ASTRs. Furt her characterization of the expression and utilization of MMPs and their in hibitors 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.