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- Title
Effect of hypoxia on the expression of αB-crystallin in head and neck squamous cell carcinoma.
- Authors
van de Schootbrugge, Chantal; Schults, Elisabeth Mj; Bussink, Johan; Span, Paul N; Grénman, Reidar; Pruijn, Ger Jm; Kaanders, Johannes Ham; Boelens, Wilbert C; Schults, Elisabeth M J; Pruijn, Ger J M; Kaanders, Johannes H A M
- Abstract
<bold>Background: </bold>The presence of hypoxia in head and neck squamous cell carcinoma (HNSCC) is associated with therapeutic resistance and increased risk of metastasis formation. αB-crystallin (HspB5) is a small heat shock protein, which is also associated with metastasis formation in HNSCC. In this study, we investigated whether αB-crystallin protein expression is increased in hypoxic areas of HNSCC biopsies and analyzed whether hypoxia induces αB-crystallin expression in vitro and in this way may confer hypoxic cell survival.<bold>Methods: </bold>In 38 HNSCC biopsies, the overlap between immunohistochemically stained αB-crystallin and pimonidazole-adducts (hypoxiamarker) was determined. Moreover, expression levels of αB-crystallin were analyzed in HNSCC cell lines under hypoxia and reoxygenation conditions and after exposure to reactive oxygen species (ROS) and the ROS scavenger N-acetylcysteine (NAC). siRNA-mediated knockdown was used to determine the influence of αB-crystallin on cell survival under hypoxic conditions.<bold>Results: </bold>In all biopsies αB-crystallin was more abundantly present in hypoxic areas than in normoxic areas. Remarkably, hypoxia decreased αB-crystallin mRNA expression in the HNSCC cell lines. Only after reoxygenation, a condition that stimulates ROS formation, αB-crystallin expression was increased. αB-crystallin mRNA levels were also increased by extracellular ROS, and NAC abolished the reoxygenation-induced αB-crystallin upregulation. Moreover, it was found that decreased αB-crystallin levels reduced cell survival under hypoxic conditions.<bold>Conclusions: </bold>We provide the first evidence that hypoxia stimulates upregulation of αB-crystallin in HNSCC. This upregulation was not caused by the low oxygen pressure, but more likely by ROS formation. The higher expression of αB-crystallin may lead to prolonged survival of these cells under hypoxic conditions.
- Publication
BMC Cancer, 2014, Vol 14, Issue 1, p252
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/1471-2407-14-252