Diffuse brain invasion of glioma cells requires β1 integrins

Werner Paulus, Inge Baur, Andreas S. Beutler, Steven A. Reeves

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Diffuse invasion of brain tissue by single tumor cells is a characteristic feature of gliomas and a major reason why these tumors cannot be completely resected. The molecular basis of brain invasion is poorly understood. We regulated the expression of β1 integrins, the major group of extracellular matrix receptors, in astrocytic tumor cells by using a tetracycline-dependent transcription control system. Rat C6 glioma cells were stably transfected with (a) the tetracycline-controlled transactivator (tTA) gene, (b) an antisense β1 cDNA under the control of a tTA/tetracycline- responsive promoter, and (c) the β-galactosidase (lacZ) gene for histochemical identification. In one clone, C6TLβ, β1 protein levels were unaffected in the presence of tetracycline, but they were reduced by 60% in the absence of tetracycline because of production of antisense mRNA. C6TLβ cells were transplanted into the striatum of nude mice. After 14 days in the presence of tetracycline in the drinking water, tumors showed diffuse brain invasion, mainly along vascular basement membranes. In the absence of tetracycline, however, tumor cells were compact and generally well delineated from the surrounding brain tissue. These data, ie, blocking of brain invasion by antisense β1 mRNA, either because of disturbed interaction of β1 with brain extracellular matrix components or interference with β1-dependent signaling pathways, strongly suggest that β1 integrins are required for diffuse brain invasion of gliomas.

Original languageEnglish (US)
Pages (from-to)819-826
Number of pages8
JournalLaboratory Investigation
Volume75
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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