Open Access

Differential expression of HIF-1 in glioblastoma multiforme and anaplastic astrocytoma

  • Authors:
    • Arnulf Mayer
    • Fabienne Schneider
    • Peter Vaupel
    • Clemens Sommer
    • Heinz Schmidberger
  • View Affiliations

  • Published online on: July 16, 2012     https://doi.org/10.3892/ijo.2012.1555
  • Pages: 1260-1270
  • Copyright: © Mayer et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Hypoxia is an important factor mediating tumor progression and therapeutic resistance, in part through proteome changes mediated by the transcription factor hypoxia-inducible factor (HIF)-1. Since glioblastoma multiforme is the epitome of a highly aggressive tumor entity, while lower-grade astrocytomas often show a prolonged clinical course, a profound difference in the extent of hypoxic tissue areas and corresponding magnitude of HIF-1 activity may exist between these entities. In this study, to address this question, serial sections of 11 glioblastomas and 10 anaplastic astrocytomas were immunostained for HIF-1α, glucose transporter (GLUT)-1, carbonic anhydrase (CA) IX (i.e., hypoxia-related markers), Ki67 (proliferation), phosphorylated ribosomal protein S6 [p-rpS6; mammalian target of rapamycin (mTOR) activity] and CD34 (microvascular endothelium). Digital scans of whole tumor sections were registered to achieve geometric correspondence for subsequent morphometric operations. HIF-1α-, GLUT-1- and CA IX-positive staining was found in all 11 glioblastomas, showing a preferential expression in tissue areas adjacent to necroses. A considerable spatial overlap between GLUT-1 and CA IX, and a colocalization of these proteins with areas of enlarged mean diffusion distances were observed. Conversely, 8 of the 10 anaplastic astrocytomas were completely negative for hypoxia-related markers. The glioblastomas also showed significantly greater heterogeneity of intercapillary distances, larger diffusion-limited tissue fractions, significantly higher mTOR activity and a trend for higher proliferation rates. Microregionally, mTOR and proliferation showed a significant spatial overlap with areas of shorter mean diffusion distances. In conclusion, diffusion-limited hypoxia, leading to the expression of hypoxia-related markers is a pivotal element of the glioblastoma phenotype and may be driven by dysregulated growth and proliferation in normoxic subregions.

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October 2012
Volume 41 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Mayer, A., Schneider, F., Vaupel, P., Sommer, C., & Schmidberger, H. (2012). Differential expression of HIF-1 in glioblastoma multiforme and anaplastic astrocytoma. International Journal of Oncology, 41, 1260-1270. https://doi.org/10.3892/ijo.2012.1555
MLA
Mayer, A., Schneider, F., Vaupel, P., Sommer, C., Schmidberger, H."Differential expression of HIF-1 in glioblastoma multiforme and anaplastic astrocytoma". International Journal of Oncology 41.4 (2012): 1260-1270.
Chicago
Mayer, A., Schneider, F., Vaupel, P., Sommer, C., Schmidberger, H."Differential expression of HIF-1 in glioblastoma multiforme and anaplastic astrocytoma". International Journal of Oncology 41, no. 4 (2012): 1260-1270. https://doi.org/10.3892/ijo.2012.1555