Modified expression of Mts1/S100A4 protein in C6 glioma cells or surrounding astrocytes affects migration of tumor cells in vitro and in vivo

Neurobiol Dis. 2007 Mar;25(3):455-63. doi: 10.1016/j.nbd.2006.10.021. Epub 2007 Jan 12.


The calcium-binding Mts1/S100A4 protein plays an important role in motility and metastatic activity of tumor cells. Recently we showed that Mts1/S100A4 is expressed in white matter astrocytes and influences their migration in vitro and in vivo. Here, we have investigated the role of Mts1/S100A4 expression in C6 glioma cells or surrounding astrocytes for migration of C6 cells on astrocytes, using short interference (si) RNA to silence Mts1/S100A4 expression. We find that in vitro, the migration of Mts1/S100A4 expressing and silenced C6 cells on astrocytes is predominantly dependent on the expression of Mts1/S100A4 in astrocytes, i.e. C6 cells preferably migrate on Mts1/S100A4-silenced astrocytes. In vivo, Mts1/S100A4-positive C6 cells preferably migrate in white matter. In contrast Mts1/S100A4-silenced C6 cells avoid white matter and migrate in gray matter and meninges. Thus, the migration pattern of C6 cells is affected by their intrinsic Mts1/S100A4 expression as well as Mts1/S100A4 expression in astrocytes. To investigate if Mts1/S100A4 has a significant role on brain tumor progression, we made quantitative RT-PCR analysis for the expression of S100A4/Mts1 in various grades of astrocytic tumors. Our data showed that high-grade glioblastomas express higher amount of S100A4/Mts1 than low-grade astrocytic tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Astrocytoma / metabolism
  • Astrocytoma / pathology*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Communication
  • Cell Line, Tumor
  • Cell Movement*
  • Corpus Callosum / metabolism
  • Corpus Callosum / pathology
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Metalloproteases / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Nerve Fibers, Myelinated / metabolism
  • Nerve Fibers, Myelinated / pathology
  • RNA, Small Interfering
  • Rats
  • S100 Calcium-Binding Protein A4
  • S100 Proteins / genetics
  • S100 Proteins / metabolism*


  • RNA, Small Interfering
  • S100 Calcium-Binding Protein A4
  • S100 Proteins
  • S100a4 protein, rat
  • S100A4 protein, human
  • Metalloproteases