Cole, L. M., Djidja, M. C., Bluff, J., Claude, E., Carolan, V. A., Paley, M., Tozer, G. M., Clench, M. R. (2011) Investigation of protein induction in tumour vascular targeted strategies by MALDI MSI. METHODS, 54 (4). pp. 442-453. ISSN 1046-2023

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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 the 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 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. (C) 2011 Elsevier Inc. All rights reserved.

Item Type:	Article
All Authors:	Cole, L. M., Djidja, M. C., Bluff, J., Claude, E., Carolan, V. A., Paley, M., Tozer, G. M., Clench, M. R.
Additional Information:	ISI Document Delivery No.: 810UD Times Cited: 0 Cited Reference Count: 28 Cole, L. M. Djidja, M-C. Bluff, J. Claude, E. Carolan, V. A. Paley, M. Tozer, G. M. Clench, M. R. Cr-uk/epsrc/mrc/nihr[c1276/a10345] This work was supported by CR-UK/EPSRC/MRC/NIHR Imaging Programme Grant C1276/A10345. Academic press inc elsevier science San diego
Uncontrolled Keywords:	Matrix-Assisted Laser Desorption/Ionisation Mass Spectrometry Imaging Bottom up proteomics Vascular disrupting agent Combretastatin A-4-3-O-phosphate (CA-4-P/Zybrestat (TM)) Haemorrhage Angiogenesis imaging mass-spectrometry disrupting agents tissue-sections
Depositing User:	Alexander Smithson
Date Deposited:	12 Sep 2011 14:34
Last Modified:	12 Sep 2011 14:34
URI:	http://publications.icr.ac.uk/id/eprint/11000

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