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Adaptive changes of glioblastoma cells following exposure to hypoxic (1% oxygen) tumour microenvironment.

  • Ahmed Musah-Eroje
    ,
  • Sue Watson
  • University of Nottingham
Research Output: Contribution to journal Article Peer-review

Open access

Abstract

Glioblastoma multiforme is the most aggressive and malignant primary brain tumour, with a median survival rate of between 15 to 17 months. Heterogeneous regions occur in glioblastoma as a result of oxygen gradients which ranges from 0.1% to 10% in vivo. Emerging evidence suggests that tumour hypoxia leads to increased aggressiveness and chemo/radio resistance. Yet, few in vitro studies have been performed in hypoxia. Using three glioblastoma cell-lines (U87, U251, and SNB19), the adaptation of glioblastoma cells in a 1% (hypoxia) and 20% (normoxia) oxygen microenvironment on proliferation, metabolism, migration, neurosphere formation, CD133 and VEGF expression was investigated. Compared to cells maintained in normoxia (20% oxygen), glioblastoma cells adapted to 1% oxygen tension by reducing proliferation and enhancing metabolism. Both migratory tendency and neurosphere formation ability were greatly limited. In addition, hypoxic-mediated gene upregulation (CD133 and VEGF) was reversed when cells were removed from the hypoxic environment. Collectively, our results reveal that hypoxia plays a pivotal role in changing the behaviour of glioblastoma cells. We have also shown that genetic modulation can be reversed, supporting the concept of reversibility. Thus, understanding the degree of oxygen gradient in glioblastoma will be crucial in personalising treatment for glioblastoma patients.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 2091

Journal (Volume, Issue Number)

International Journal of Molecular Sciences (Volume 20, Issue 9)

Publication milestones

  • Accepted/In press - 24/04/2019
  • Published - 28/04/2019

Publication status

Published - 28/04/2019

ISSN

1661-6596

External Publication IDs

  • handle.net: 10547/623622
  • Scopus: 85065473750

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