Cerebral microenvironment influences expression of the vitronectin gene in astrocytic tumors.

  • Gladson C
  • Wilcox J
  • Sanders L
 et al. 
  • 26

    Readers

    Mendeley users who have this article in their library.
  • 117

    Citations

    Citations of this article.

Abstract

Expression of the vitronectin gene was detected in advanced human astrocytoma by in situ hybridization, whereas vitronectin mRNA was undetectable in low grade tumors or in normal adult brain, indicating that vitronectin is a marker of malignant astrocytoma. We established a model of human astrocytoma by transplanting U-251MG human astrocytoma cells intracerebrally into acid mice (C.B.17 severe combined immunodeficient mice). In this model, tumors progressed rapidly and vitronectin mRNA was preferentially detected at the invading tumor margins, i.e. where tumor cells were adjacent to the normal brain tissue. Surprisingly, when U-251MG cells were injected subcutaneously into scid mice, vitronectin mRNA was undetectable throughout the tumor. Moreover, vitronectin mRNA or protein could not be detected among these cells in culture under a wide variety of growth conditions. These findings demonstrate that the cerebral microenvironment influences the expression of the vitronectin gene in malignant astrocytoma. Importantly, the vitronectin binding integrins alpha v beta 3 and alpha v beta 5 localized to distinct sites within these tumors, with beta 3 mRNA synthesized among invading cells, and alpha v and beta 5 mRNAs detected throughout the tumor. In vitro, both of these receptors were capable of promoting adhesion and invasion of astrocytoma cells on a vitronectin substratum. These findings implicate the expression of the vitronectin gene as a contributing factor to the biological behavior of astrocytomas within the cerebral microenvironment.

Author-supplied keywords

  • astrocytoma
  • integrin
  • microenvironment
  • vitronectin

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • C L Gladson

  • J N Wilcox

  • L Sanders

  • G Y Gillespie

  • D a Cheresh

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free