Abstract
MALDI imaging mass spectrometry is an evolving technology capable of simultaneously profiling multiple analytes of interest across a tissue section and aligning their distribution to tissue histopathology. This chapter summarizes a MALDI imaging workflow for on-tissue identification of sphingolipids and glycosphingolipids using tissues derived from mouse models known to accumulate ceramides (Farber disease) and globotriaosylceramides (Fabry disease). A combination of CID and on-tissue enzyme digestions was utilized for structural confirmation prior to being added to the comprehensive sphingolipid and glycosphingolipid library. Two example case studies related to the modulation of sphingolipid metabolism are provided to illustrate the potential applications of MALDI imaging. In the first case study, distinct ceramides were visualized in relation to Lewis lung carcinoma tumors. In the second case study, tissues were derived from a tumor xenograft model treated with a drug targeting the sphingosine-1-phosphate/ceramide nexus. Representative images of ceramide and hexose ceramides in relation to cancer alone or drug distribution correlating to an increase or decrease in sphingosine-1-phosphate or ceramide species are provided. These MALDI imaging workflows can be readily adapted to assess the distribution of sphingolipids and glycosphingolipids in any tissue system of interest.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Larsen PJ, Tennagels N (2014) On ceramides, other sphingolipids and impaired glucose homeostasis. Mol Metab 28:252–260
Hannon YA, Obeid LM (2011) Many ceramides. J Biol Chem 286:27855–27862
Morad SA, Cabot MC (2013) Ceramide-orchestrated signaling in cancer cells. Nat Rev Cancer 13:51–65
Beckham TH, Lu P, Jones EE et al (2013) LCL124, a cationic analog of ceramide, selectively induces pancreatic cancer cell death by accumulating in mitochondria. J Pharmacol Exp Ther 344:167–178
Saddoughi SA, Ogretman B (2013) Diverse functions of ceramide in cancer cell death and proliferation. Adv Cancer Res 117:37–58
Ponnusamy S, Meyers-Needham M, Senkal CE et al (2012) Sphingolipids and cancer: ceramide and sphingosine-1-phosphate in the regulation of cell death and drug resistance. EMBO Mol Med 8:761–765
Slotte JP (2013) Biological functions of sphingomyelins. Prog Lipid Res 52:424–437
Vouk K, Hevir N, Ribic-Pucelj M et al (2012) Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis. Hum Reprod 27:2955–2965
Zhu J, Wang Y, Yu Y et al (2013) Aberrant fucosylation of glycosphingolipids in human hepatocellular carcinoma tissues. Liver Int 34:147–160
Liu Y, Chen Y, Momin A et al (2010) Elevation of sulfatides in ovarian cancer: an integrated transcriptomic and lipidomic analysis including tissue-imaging mass spectrometry. Mol Cancer 9:186
Schwamborn K, Caprioli RM (2010) MALDI Imaging mass spectrometry—painting molecular pictures. Nat Rev Cancer 10:639–646
Irie M, Fujimura Y, Yamato M et al (2014) Integrated MALDI-MS imaging and LC-MS techniques for visualizing spatiotemporal metabolomics dynamics in a rat stroke model. Metabolomics 10:473–483
Jones EE, Dworski S, Canals D et al (2014) On tissue localization of ceramides and other sphingolipids by MALDI mass spectrometry imaging. Anal Chem 19:8303–8311
Stoeckli M, Chaurand P, Hallahan DE et al (2001) Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat Med 4:493–496
Gessel MM, Norris JL, Caprioli RM (2014) MALDI imaging mass spectrometry: spatial molecular analysis to enable a new age of discovery. J Proteomics 107:71–82
Berry KA, Hankin JA, Barkley RM et al (2011) MALDI imaging of lipid biochemistry in tissues by mass spectrometry. Chem Rev 111:6491–6512
Angel PM, Spraggins JM, Baldwin HS et al (2012) Enhanced sensitivity for high spatial resolution lipid analysis by negative ion mode matrix assisted laser desorption ionization imaging mass spectrometry. Anal Chem 84:1557–1564
Sun N, Ly A, Meding S et al (2014) High-resolution metabolite imaging of light and dark treated retina using MALDI-FTICR mass spectrometry. Proteomics 7–8:913–923
Wang X, Han J, Pan J et al (2014) Comprehensive imaging of porcine adrenal gland lipids by MALDI-FTMS using quercetin as a matrix. Anal Chem 86:638–646
Chen Y, Liu Y, Sullards MC et al (2010) An introduction to sphingolipid metabolism and analysis by new technologies. Neuromolecular Med 12:306–319
Powers TW, Jones EE, Betesh LR et al (2013) A MALDI imaging mass spectrometry workflow for spatial profiling analysis of N-linked glycan expression in tissues. Anal Chem 20:9799–9806
Chaurand P, Cornett DS, Angel PM, Caprioli RM (2011) From whole-body sections down to cellular level, multiscale imaging of phospholipids by MALDI mass spectrometry. Mol Cell Proteomics 10:O110.004259
Castellino S, Groseclose MR, Sigafoos J et al (2012) Central Nervous system disposition and metabolism of Fosdevirine (GSK2248761), a non-nucleoside reverse transcriptase inhibitor: an LC-MS Matrix-assisted laser desorption/ionization imaging MS investigation into central nervous system toxicity. Chem Res Toxicol 2:241–251
Chughtai K, Jiang L, Greenwood TR et al (2013) Mass spectrometry images acylcarnitines, phosphatidylcholines, and sphingomyelin in MDA-MB-231 breast tumor models. J Lipid Res 54:333–344
Chaurand P, Cornett DS, Angel PM et al (2011) From whole-body sections down to cellular level, multiscale imaging of phospholipids by MALDI mass spectrometry. Mol Cell Proteomics 2:o110.004259
Chen Y, Liu Y, Allegood J et al (2010) Imaging MALDI mass spectrometry of sphingolipids using an oscillating capillary nebulizer matrix application system. Methods Mol Biol 656:131–146
Chen Y, Allegood J, Liu Y et al (2008) Imaging MALDI mass spectrometry using an oscillating capillary nebulizer matrix coating system and its application to analysis of lipids in brain from a mouse model of Tay-Sachs/Sandhoff disease. Anal Chem 80(8):2780–2788
Le CH, Han J, Borchers CH et al (2012) Dithranol as a MALDI matrix for tissue imaging of lipids by Fourier transform ion cyclotron resonance mass spectrometry. PLoS One 7(11), e49519
Fulop A, Porada MB, Marsching C et al (2013) 4-Phenyl-α-cyanocinnamic acid amide: screening for a negative ion matrix for MALDI-MS imaging of multiple lipid classes. Anal Chem 85:9156–9163
Cerruti CD, Touboul D, Guerineau V et al (2011) MALDI imaging mass spectrometry of lipids by adding lithium salts to the matrix solution. Anal Bioanal Chem 401:75–87
Goto-Inoue N, Hayasaka T et al (2010) The detection of glycosphingolipids in brain tissue sections by imaging mass spectrometry using gold nanoparticles. J Am Soc Mass Spectrom 11:1940–1943
Goto-Inoue N, Hayasaka T, Zaima N et al (2012) Imaging mass spectrometry visualizes ceramides and the pathogenesis of dorfman-chanarin syndrome due to ceramide metabolic abnormality in the skin. PLoS One 7(11), e49519
Colsch B, Woods AS (2010) Localization and imaging of sialylated glycosphingolipds in brain tissue sections by MALDI mass spectrometry. Glycobiology 6:661–667
Alayoubi AM, Wang JC, Au BC et al (2013) Systemic ceramide accumulation leads to severe and varied pathological consequences. EMBO Mol Med 5:827–842
Pacienza N, Yoshitmitsu M, Mizue N et al (2012) Lentivector transduction improves outcomes over transplantation of human HSCs alone in NOD/SCID/Fabry mice. Mol Ther 7:1454–1461
Baykut G, Fuchser J, Witt M et al (2002) A combined ion source for fast switching between electrospray and matrix-assisted laser desorption/ionization in Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun Mass Spectrom 16:1631–1641
O’Connor PB, Costello CE (2001) A high pressure matrix-assisted laser desorption/ionization Fourier transform mass spectrometry ion source for thermal stabilization of labile biomolecules. Rapid Commun Mass Spectrom 15:1862–1868
O’Connor PB, Mirgorordskaya E, Costello CE (2002) High pressure matrix-assisted laser desorption/ionization Fourier transform mass spectrometry for minimization of ganglioside fragmentation. J Am Soc Mass Spectrom 13:402–407
Pettus BJ, Bielawska A, Kroesen BJ et al (2003) Observation of different ceramide species from crude cellular extracts by normal-phase high-performance liquid chromatography coupled to atmospheric pressure chemical ionization mass spectrometry. Rapid Commun Mass Spectrom 17:1203–1211
Canals D, Hannun YA (2013) Novel chemotherapeutic drugs in sphingolipid cancer research. Handb Exp Pharmacol 211–38
Nowling TK, Mather AR, Thirumagal T et al (2015) Renal glycosphingolipid metabolism is dysfunctional in lupus mice and patients with nephritis. J Am Soc Nephrol 26:1402
Whitehead SN, Chan KH, Gangaraju S et al (2011) Imaging mass spectrometry detection of gangliosides species in the mouse brain following transient focal cerebral ischemia and long-term recovery. PLoS One 6, e20808
Grove KJ, Voziyan PA, Spraggins JM et al (2014) Diabetic nephropathy induces alterations in the glomerular and tubule lipid profiles. J Lipid Res 55:1375–1385
Woods AS, Colsch B, Jackson SN et al (2013) Gangliosides and ceramides change in a mouse model of blast induced traumatic brain injury. ACS Chem Neurosci 4:594–600
Richards AL, Lietz CB, Wager-Miller J et al (2012) Localization and imaging of gangliosides in mouse brain tissue sections by laserspray ionization inlet. J Lipid Res 53:1390–1398
Honke K, Zhang Y, Cheng X et al (2004) Biological roles of sulfoglycolipids and pathophysiology of their deficiency. Glycoconj J 21:59–62
Yuki D, Sugiura Y, Zaima N et al (2011) Hydroxylated and non-hydroxylated sulfatide are distinctly distributed in the human cerebral cortex. Neuroscience 193:44–53
Marsching C, Eckhardt M, Grone H et al (2011) Imaging of complex sulfatides SM3 and SB1a in mouse kidney using MALDI-TOF/TOF mass spectrometry. Anal Bioanal Chem 401:53–64
Manwaring V, Boutin M, Auray-Blais C (2013) A metabolomic study to identify new globotriaosylceramide-related biomarkers in the plasma of Fabry disease patients. Anal Chem 19:9039–9048
Yamaura T, Doki Y, Murakami K, Saiki I (1999) Model for mediastinal lymph node metastasis produced by orthotopic intrapulmonary implantation of lung cancer cells in mice. Hum Cell 12:197–204
Giussani P, Tringali C, Riboni L et al (2014) Sphingolipids: key regulators of apoptosis and pivotal players in cancer drug resistance. Int J Mol Sci 3:4356–4392
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Jones, E.E. et al. (2015). Detection and Distribution of Sphingolipids in Tissue by FTICR MALDI-Imaging Mass Spectrometry. In: Hannun, Y., Luberto, C., Mao, C., Obeid, L. (eds) Bioactive Sphingolipids in Cancer Biology and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-20750-6_15
Download citation
DOI: https://doi.org/10.1007/978-3-319-20750-6_15
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-20749-0
Online ISBN: 978-3-319-20750-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)