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Role of intracellular S100A4 for migration of rat astrocytes
Author(s) -
Takenaga Keizo,
Kozlova Ele.
Publication year - 2006
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20284
Subject(s) - biology , astrocyte , intracellular , microbiology and biotechnology , glioma , extracellular , downregulation and upregulation , neuroglia , cell migration , motility , transfection , small interfering rna , white matter , matrix metalloproteinase , cell culture , neuroscience , in vitro , cancer research , central nervous system , medicine , biochemistry , genetics , radiology , gene , magnetic resonance imaging
S100A4 is a member of the EF‐hand family of calcium‐binding proteins, first identified in tumor cells, and implicated in tumor invasion and metastasis. Intracellular upregulation of S100A4 is associated with increased motility of tumor cells. Extracellular application of S100A4 increases the motility of glioma cells in vitro. We showed previously that astrocytes in spinal cord and brain white matter also express S100A4. This expression is markedly increased in reactive white matter astrocytes after injury. Here, we have explored how changes in intracellular S100A4 affect migration of astrocytes. We produced cultures of white matter, S100A4 expressing astrocytes, and developed a small interfering (si) RNA approach to specifically eliminate S100A4 expression in these cells, and compared the migration of astrocytes expressing S100A4 with astrocytes transfected with S100A4 siRNA. As a “positive control” we used S100A4 expressing C6 glioma cells. In contrast to malignant cells, S100A4 expressing astrocytes increased their migration capacity after S100A4 siRNA treatment. At the same time, and in parallel with increased migration, white matter astrocytes increased their expression of metalloproteinases MMP‐9 and MT1‐MMP. The addition of MMP‐2/MMP‐9 inhibitor resulted in a significant inhibition of migration in S100A4 siRNA‐treated astrocytes. These findings indicate that S100A4 has a stabilizing function in reactive white matter astrocytes, a function that may contribute to the development of a rigid, growth‐inhibitory glial scar. © 2005 Wiley‐Liss, Inc.