Stimulation of extracellular matrix components in the normal brain by invading glioma cells

  • Knott J
  • Mahesparan R
  • Garcia-Cabrera I
 et al. 
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Malignant gliomas are characterized by an extensive inva- sion of tumor cells into the normal brain parenchyma. A substantial amount of data indicates that cell movement in general is regulated by specific interactions between extracel- lular matrix components and specific cell-surface receptors. In the present work, multicellular spheroids from 4 human glioma cell lines (U-373Mg, A-172Mg, U-251Mg and HF-66) were confronted with normal rat brain cell aggregates in vitro, which resulted in a progressive invasion of tumor cells into the brain aggregates. The co-cultures were then sec- tioned and immuno-stained for specific extracellular matrix components (laminin, fibronectin and collagen type IV) and for specific cell-surface receptors which bind to these compo- nents (integrins 1, 4, 3, 6). In addition, flow-cytometric measurements and Northern blot analyses showed expres- sion of several different integrins within the cell lines. The 3 subunit was expressed strongly in all cell lines. Whereas the 1 subunit was expressed weakly in exponentially growing monolayer cultures, it showed a pronounced expression in multicellular spheroids, indicating that the integrin expres- sion may vary depending on the micro-environment within a tumor. Furthermore, normal brain tissue was able to pro- duce laminin when confronted with the glioma cells, which also was observed for fibronectin and collagen type IV. The relevance of our observations to the in vivo situation was investigated further by immuno-staining 5 human glioma biopsy samples for laminin. In some areas of the tumors, specific deposits of laminin were observed. In conclusion, we have shown that normal brain tissue has the ability to produce extracellular matrix components, such as laminin, collagen type IV and fibronectin, when confronted with invading glioma cells. Our results show that the glioma cells express specific integrins which can interact with these extracellular matrix components. Such interactions may facilitate tumor cell migration and invasion. Int. J. Cancer 75:864–872, 1998

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  • Jo C.A. Knott

  • Rupavathana Mahesparan

  • Inmaculada Garcia-Cabrera

  • Berit Bølge Tynes

  • Klaus Edvardsen

  • Gro Oddveig Ness

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