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Neoplasma Vol.50, p.251-256, 2003 |
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Title: High cell density-mediated pericellular hypoxia is a crucial factor inducing expression of the intrinsic hypoxia marker CA IX in vitro in HeLa cells. | ||
Author: A., CHRASTINA ; | ||
Abstract: Oxygen plays a central role in respiration of the cells and thus in generation
of energy by aerobic metabolism. The cells precisely detect oxygen level and
changes in oxygen perfusion leads to induction of various responses enabling to
adapt to unfavorable conditions. CA IX carbonic anhydrase is a hypoxia-inducible
tumor-associated antigen which is overexpressed in dense HeLa cells. Presented
study investigates the effects of oxygen tension on CA IX expression in HeLa
cell culture. Using of an immunoradiometric assay to quantify CA IX protein, it
was revealed that expression of CA IX correlates with increasing cell density,
lactate production and medium acidification under normoxic conditions. These
observations and hypoxia-inducibility of CA IX suggested a possible role of
pericellular hypoxia in density-induced CA IX expression. To test this
hypothesis, HeLa cells were incubated in normobaric hyperoxia (50% O2) or cell
culture medium was convected to disturb oxygen deprivation. Both approaches
completely abrogated CA IX expression in dense HeLa cell cultures and therefore
confirmed the importance of decreased oxygen tension in high cell
density-induced CA IX expression. In addition, HeLa cells exposed to hyperoxia
retained inducibility of CAIX expression by transition metals and iron
chelators, suggesting that they act independently of cell density
mediated-pO2-gradient or at a downstream site from oxygen sensor. Observed data
indicate that high cell density-lowered pericellular pO2 is a crucial factor
inducing CA IX expression and influencing composition of metabolic micromilieu
surrounding the dense HeLa cells.
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Year: 2003, Volume: 50, Issue: | Page From: 251, Page To: 256 | |
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