Lipid Profiles of Canine Invasive Transitional Cell Carcinoma of the Urinary Bladder and Adjacent Normal Tissue by Desorption Electrospray Ionization Imaging Mass Spectrometry

Allison L. Dill†, Demian R. Ifa†, Nicholas E. Manicke†, Anthony B. Costa†, José A. Ramos-Vara§, Deborah W. Knapp‡ and R. Graham Cooks*†
Department of Chemistry and Center for Analytical Instrumentation Development, Department of Veterinary Clinical Sciences, Department of Comparative Pathobiology, and Purdue Cancer Center, Purdue University, West Lafayette, Indiana 47907
Anal. Chem., 2009, 81 (21), pp 8758–8764
DOI: 10.1021/ac901028b
Publication Date (Web): October 7, 2009
Copyright © 2009 American Chemical Society
* Corresponding author. Tel: (765) 494-5262. Fax: (765) 494-9421. E-mail: cooks@purdue.edu., †

Department of Chemistry and Center for Analytical Instrumentation Development.

, §

Department of Comparative Pathobiology.

, ‡

Department of Veterinary Clinical Sciences.

,

Purdue Cancer Center.

Biochemical Methods

Abstract

Desorption electrospray ionization mass spectrometry (DESI-MS) was used in an imaging mode to interrogate the lipid profiles of thin tissue sections of canine spontaneous invasive transitional cell carcinoma of the urinary bladder (a model of human invasive bladder cancer) as well as adjacent normal tissue from four different dogs. The glycerophospholipids and sphingolipids that appear as intense signals in both the negative ion and positive ion modes were identified by tandem mass spectrometry product ion scans using collision-induced dissociation. Differences in the relative distributions of the lipid species were present between the tumor and adjacent normal tissue in both the negative and positive ion modes. DESI-MS images showing the spatial distributions of particular glycerophospholipids, sphinoglipids, and free fatty acids in both the negative and positive ion modes were compared to serial tissue sections that were stained with hematoxylin and eosin (H&E). Increased absolute and relative intensities for at least five different glycerophospholipids and three free fatty acids in the negative ion mode and at least four different lipid species in the positive ion mode were seen in the tumor region of the samples in all four dogs. In addition, one sphingolipid species exhibited increased signal intensity in the positive ion mode in normal tissue relative to the diseased tissue. Principal component analysis was also used to generate unsupervised statistical images from the negative ion mode data, and these images are in excellent agreement with the DESI images obtained from the selected ions and also the H&E-stained tissue.

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History

  • Published In Issue November 01, 2009
  • Article ASAPOctober 07, 2009
  • Received: May 12, 2009
    Accepted: September 22, 2009

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