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

Autor: Harrison H; Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK. hannah.harrison@manchester.ac.uk., Pegg HJ; Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK., Thompson J; Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK., Bates C; Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK., Shore P; Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK. paul.shore@manchester.ac.uk.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2018 Jun 20; Vol. 18 (1), pp. 674. Date of Electronic Publication: 2018 Jun 20.
DOI: 10.1186/s12885-018-4577-1
Abstrakt: Background: Hypoxia 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.
Methods: We 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.
Results: We 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.
Conclusions: These 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.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje