Papaevangelou, E; Whitley, GS; Johnstone, AP; Robinson, SP; Howe, FA
(2016)
Investigating the role of tumour cell derived iNOS on tumour growth and vasculature in vivo using a tetracycline regulated expression system.
International Journal of Cancer, 138 (11).
pp. 2678-2687.
ISSN 1097-0215
https://doi.org/10.1002/ijc.29997
SGUL Authors: Howe, Franklyn Arron
Abstract
Nitric oxide (NO) is a free radical signalling molecule involved in various physiological and pathological processes, including cancer. Both tumouricidal and tumour promoting effects have been attributed to NO, making its role in cancer biology controversial and unclear. To investigate the specific role of tumour-derived NO in vascular development, C6 glioma cells were genetically modified to include a doxycycline regulated gene expression system that controls the expression of an antisense RNA to inducible nitric oxide synthase (iNOS) in order to manipulate endogenous iNOS expression. Xenografts of these cells were propagated in the presence or absence of doxycycline. Susceptibility magnetic resonance imaging (MRI), initially with a carbogen (95% O2 /5% CO2 ) breathing challenge and subsequently an intravascular blood pool contrast agent, was used to assess haemodynamic vasculature (ΔR2 *) and fractional blood volume (fBV), and correlated with histopathological assessment of tumour vascular density, maturation and function. Inhibition of NO production in C6 gliomas led to significant growth delay and inhibition of vessel maturation. Parametric fBV maps were used to identify vascularised regions, from which the carbogen-induced ΔR2 * was measured and found to be positively correlated with vessel maturation, quantified ex vivo using fluorescence microscopy for endothelial and perivascular cell staining. These data suggest that tumour-derived iNOS is an important mediator of tumour growth and vessel maturation, hence a promising target for anti-vascular cancer therapies. The combination of ΔR2 * response to carbogen and fBV MRI can provide a marker of tumour vessel maturation that could be applied to non-invasively monitor treatment response to iNOS inhibitors. This article is protected by copyright. All rights reserved.
Item Type: |
Article
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Additional Information: |
This is the peer reviewed version of the following article: Papaevangelou, E; Whitley, GS; Johnstone, AP; Robinson, SP; Howe, FA (2016) Investigating the role of tumour cell derived iNOS on tumour growth and vasculature in vivo using a tetracycline regulated expression system. International Journal of Cancer, 138 (11). pp. 2678-2687. ISSN 1097-0215 10.1002/ijc.29997, which has been published in final form at https://doi.org/10.1002/ijc.29997 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
Keywords: |
MRI, inducible expression, nitric oxide, nitric oxide synthase, tumour vessel maturation, Oncology & Carcinogenesis, 1112 Oncology And Carcinogenesis |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Neuroscience (INCCNS) |
Journal or Publication Title: |
International Journal of Cancer |
ISSN: |
1097-0215 |
Language: |
ENG |
Dates: |
Date | Event |
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14 March 2016 | Published | 8 February 2016 | Published Online | 16 December 2015 | Accepted |
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PubMed ID: |
26756734 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/107609 |
Publisher's version: |
https://doi.org/10.1002/ijc.29997 |
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