Investigation of protein induction in tumour vascular targeted strategies by MALDI MSI

COLE, Laura, DJIDJA, M-C, BLUFF, J., CLAUDE, E, CAROLAN, Vikki, PALEY, M, TOZER, G M and CLENCH, Malcolm (2011). Investigation of protein induction in tumour vascular targeted strategies by MALDI MSI. Methods, 54 (4), 442-453.

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Abstract

Characterising the protein signatures in tumours following vascular-targeted therapy will help determine both treatment response and resistance mechanisms. Here, mass spectrometry imaging and MS/MS with and without ion mobility separation have been used for this purpose in a mouse fibrosarcoma model following treatment with the tubulin-binding tumour vascular disrupting agent, combretastatin A-4-phosphate (CA-4-P). Characterisation of peptides after in-situ tissue tryptic digestion was carried out using Matrix Assisted Laser Desorption Ionisation- Mass Spectrometry (MALDI-MS) and Matrix Assisted Laser Desorption Ionisation- Ion Mobility Separation- Mass Spectrometry Imaging (MALDI-IMS-MSI) to observe spatial distribution of peptides. Matrix Assisted Laser Desorption Ionisation- Ion Mobility Separation- Tandem Mass Spectrometry (MALDI-IMS-MS/MS) of peaks was performed to elucidate any pharmacological responses and potential biomarkers. By taking tumour samples at a number of time points after treatment gross changes in the tissue were indicated by the changes in the signal levels of certain peptides. These were identified as arising from haemoglobin and indicated the disruption of the tumour vasculature. It was hoped that the use of PCA-DA would reveal more subtle changes taking place in the tumour samples however these are masked by the dominance of the changes in the haemoglobin signals.

Item Type:	Article
Research Institute, Centre or Group - Does NOT include content added after October 2018:	Biomedical Research Centre
Identification Number:	https://doi.org/10.1016/j.ymeth.2011.03.007
Page Range:	442-453
Depositing User:	Malcolm Clench
Date Deposited:	08 Jul 2014 09:10
Last Modified:	18 Mar 2021 06:16
URI:	https://shura.shu.ac.uk/id/eprint/8226

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