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

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Cole, Laura ; Djidja, M-C ; Bluff, J. ; Claude, E ; Carolan, Vikki ; Paley, M ; Tozer, G M ; Clench, Malcolm (2011)

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.
  • References (27)
    27 references, page 1 of 3

    1) Hanahan D and Weinberg RA (2000) The hallmarks of cancer. Cell. 100. 57- 70

    2) Lord CJ and Ashworth A (2010) Biology-driven cancer drug development: back to the future. BMC Biology. 8. (38) 1-12

    3) Kanthou and Tozer (2007) Selective destruction of the tumour vasculature by targeting the endothelial cytoskeleton. Drug discovery today: Therapeutic strategies. 4. (4) 237-243

    4) Thorpe PE, Chaplin DJ, Blakey DC (2003) The first international conference on vascular targeting: Meeting overview. Cancer Research. 63. 1144-1147

    5) Zhi-chao SI, Jie L (2008) What 'helps' tumours evade vascular targeting treatment? Chinese Medical Journal. 121. (9) 844-849

    6) Tozer GM, Kanthou C, Lewis G, Prise VE, Vojnovic B, Hill A (2008) Tumour vascular disrupting agents: combating treatment resistance. The British Journal of Radiology. 81. S12-S20

    7) Abdollahi A, Folkman J (2010) Evading tumour evasion: Current concepts and perspectives of anti-angiogenic cancer therapy. Drug Resistance Updates. 13. 16-28

    8) Kanthou C and Tozer GM (2009) Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies International Journal of Experimental Pathology 80. 284-294.

    9) Siemann W. (2009) "Vascular targeted therapies in oncology" Cell and Tissue Research 335. 241-248.

    10) Caprioli, R. M., Farmer T.B. and Gile J. (1997) Molecular Imaging of Biological Samples: Localization of Peptides and Proteins Using MALDI-TOF MS Anal. Chem. 69, 4751-4760.

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