Mr. Del Bigio et al., Expression of extracellular matrix degrading enzymes during migration of xenografted brain cells, NEUROP AP N, 25(1), 1999, pp. 54-62
Proteolytic enzymes, postulated to create an avenue for cell migration by d
igestion of host extracellular matrix molecules, have been implicated in ne
oplastic glial cell migration. A similar process is likely to occur in the
developing brain, Fetal rabbit brain fragments transplanted into the striat
um of the neonatal Shiverer mouse give rise to cells which migrate from the
graft site and differentiate into astrocytes and oligodendrocytes. Protein
ase expression by transplanted brain cells was studied using immunohistoche
mistry and in situ hybridization. Immature donor cells expressed the mRNAs
for matrix metalloproteinases (MMP) 1 (collagenase) and 3 (stromelysin), No
rthern blot analysis of rabbit brain showed that MMP-1 in particular is exp
ressed in the immature rabbit cerebrum and downregulated during maturation.
Immature donor cells exhibited immunoreactivity for urokinase plasminogen
activator, However, immunoreactivity was also present in maturing neurons.
Donor and host astroglia in the vicinity of grafts were immunoreactive for
MMP-2 and tissue-type plasminogen activator. This expression may represent
a reactive phenomenon, not specifically related to cell migration, by matur
e astrocytes, Based upon our findings, MMP-1 appears to be a candidate for
involvement in migration of immature brain cells in the cerebrum.