title: Investigation of protein induction in tumour vascular targeted strategies by MALDI MSI.
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.
authors: Biomedical Research Centre, Sheffield Hallam University, Sheffield S1 1WB, UK.
authors: L M
authors: LM
authors: Cole
authors: M-C
authors: MC
authors: Djidja
authors: J
authors: J
authors: Bluff
authors: E
authors: E
authors: Claude
authors: V A
authors: VA
authors: Carolan
authors: M
authors: M
authors: Paley
authors: G M
authors: GM
authors: Tozer
authors: M R
authors: MR
authors: Clench
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism; D005354:Fibrosarcoma / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D010449:Peptide Mapping; D011506:Proteins / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D013267:Stilbenes / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D011506:Proteins; D013267:Stilbenes; C058728:fosbretabulin