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Time‐of‐flight SIMS as a novel approach to unlocking the hypoxic properties of cancer
Author(s) -
Armitage Emily G,
Kotze Helen L,
Fletcher John S,
Henderson Alex,
Williams Kaye J,
Lockyer Nicholas P,
Vickerman John C
Publication year - 2013
Publication title -
surface and interface analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.52
H-Index - 90
eISSN - 1096-9918
pISSN - 0142-2421
DOI - 10.1002/sia.5050
Subject(s) - chemistry , spheroid , hypoxia (environmental) , multicellular organism , cancer cell , cancer research , hif1a , cell , metabolism , cancer , computational biology , biology , biochemistry , in vitro , oxygen , genetics , gene , organic chemistry
It is known that hypoxia‐inducible factor 1 (HIF‐1) activity results in the coordinated up‐regulation of a large number of proteins that facilitate cell survival in tumours; however, the effect of HIF‐1 on cancer metabolism is less well characterised. With knowledge of the specific effect of HIF‐1 on cancer metabolism, biomarkers could be identified for which new drugs could be targeted. Time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) offers the potential to analyse intact cells in situ and has a mass spectral coverage that is applicable to metabolic profiling. It has been used to analyse the effects of HIF‐1 on multicellular tumour models. Multicellular tumour spheroids (MTSs) have been cultured from human colon carcinoma cells with and without the expression of HIF‐1, and the surface of the cross sections of each MTS has been analysed. Because metabolic profiling is an emerging field in ToF‐SIMS, there is a requirement to determine which metabolites can be detected using this technique and which of those can be identified in complex mixtures within biological samples. For this, a selection of metabolites have been analysed, and the ToF‐SIMS standard spectra acquired have been used to localise metabolites in MTS sections. The comparison of metabolic profiles of MTSs with and without the expression of HIF‐1 has elucidated potential biomarkers for tumour survival in hypoxia, some of which may be HIF‐1 regulated. Copyright © 2012 John Wiley & Sons, Ltd.