HIF1-alpha expressing cells induce a hypoxic-like response in neighbouring cancer cells

Abstract

BackgroundHypoxia stimulates metastasis in cancer and is linked to poor patient prognosis. In tumours, oxygen levels vary and hypoxic regions exist within a generally well-oxygenated tumour. However, whilst the heterogeneous environment is known to contribute to metastatic progression, little is known about the mechanism by which heterogeneic hypoxia contributes to cancer progression. This is largely because existing experimental models do not recapitulate the heterogeneous nature of hypoxia.The primary effector of the hypoxic response is the transcription factor Hypoxia inducible factor 1-alpha (HIF1-alpha). HIF1-alpha is stabilised in response to low oxygen levels in the cellular environment and its expression is seen in hypoxic regions throughout the tumour.MethodsWe have developed a model system in which HIF1-alpha can be induced within a sub-population of cancer cells, thus enabling us to mimic the effects of heterogeneic HIF1-alpha expression.ResultsWe show that induction of HIF1-alpha not only recapitulates elements of the hypoxic response in the induced cells but also results in significant changes in proliferation, gene expression and mammosphere formation within the HIF1-alpha negative population.ConclusionsThese findings suggest that the HIF1-alpha expressing cells found within hypoxic regions are likely to contribute to the subsequent progression of a tumour by modifying the behaviour of cells in the non-hypoxic regions of the local micro-environment.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4577-1) contains supplementary material, which is available to authorized users.

Nitrous oxide intoxication: systematic literature review and proposal of new diagnostic possibilities

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Biomimetic Metal-Organic Framework Nanoparticles for Synergistic Combining of SDT-Chemotherapy Induce Pyroptosis in Gastric Cancer

“…HIF-1α is considered a key mediator of signal in poorly oxygenated areas and can stay steady under a hypoxia environment ( Robertson et al, 2014 ; Harrison et al, 2018 ). In normoxia conditions, HIF-1α is always inactivated and degraded so that it is hardly detected ( Masoud and Li, 2015 ).…”

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