MALDI imaging mass spectrometry for in situ proteomic analysis of preneoplastic lesions in pancreatic cancer.

The identification of new biomarkers for preneoplastic pancreatic lesions (PanINs, IPMNs) and early pancreatic ductal adenocarcinoma (PDAC) is crucial due to the diseases high mortality rate upon late detection. To address this task we used the novel technique of matrix-assisted laser desorption/ion...

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Autores principales:	Barbara M Grüner, Hannes Hahne, Pawel K Mazur, Marija Trajkovic-Arsic, Stefan Maier, Irene Esposito, Evdokia Kalideris, Christoph W Michalski, Jörg Kleeff, Sandra Rauser, Roland M Schmid, Bernhard Küster, Axel Walch, Jens T Siveke
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5384f88b088940dfbfa369db2094a494
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spelling	oai:doaj.org-article:5384f88b088940dfbfa369db2094a4942021-11-18T07:14:21ZMALDI imaging mass spectrometry for in situ proteomic analysis of preneoplastic lesions in pancreatic cancer.1932-620310.1371/journal.pone.0039424https://doaj.org/article/5384f88b088940dfbfa369db2094a4942012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22761793/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The identification of new biomarkers for preneoplastic pancreatic lesions (PanINs, IPMNs) and early pancreatic ductal adenocarcinoma (PDAC) is crucial due to the diseases high mortality rate upon late detection. To address this task we used the novel technique of matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) on genetically engineered mouse models (GEM) of pancreatic cancer. Various GEM were analyzed with MALDI IMS to investigate the peptide/protein-expression pattern of precursor lesions in comparison to normal pancreas and PDAC with cellular resolution. Statistical analysis revealed several discriminative m/z-species between normal and diseased tissue. Intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) could be distinguished from normal pancreatic tissue and PDAC by 26 significant m/z-species. Among these m/z-species, we identified Albumin and Thymosin-beta 4 by liquid chromatography and tandem mass spectrometry (LC-MS/MS), which were further validated by immunohistochemistry, western blot, quantitative RT-PCR and ELISA in both murine and human tissue. Thymosin-beta 4 was found significantly increased in sera of mice with PanIN lesions. Upregulated PanIN expression of Albumin was accompanied by increased expression of liver-restricted genes suggesting a hepatic transdifferentiation program of preneoplastic cells. In conclusion we show that GEM of endogenous PDAC are a suitable model system for MALDI-IMS and subsequent LC-MS/MS analysis, allowing in situ analysis of small precursor lesions and identification of differentially expressed peptides and proteins.Barbara M GrünerHannes HahnePawel K MazurMarija Trajkovic-ArsicStefan MaierIrene EspositoEvdokia KaliderisChristoph W MichalskiJörg KleeffSandra RauserRoland M SchmidBernhard KüsterAxel WalchJens T SivekePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39424 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Barbara M Grüner Hannes Hahne Pawel K Mazur Marija Trajkovic-Arsic Stefan Maier Irene Esposito Evdokia Kalideris Christoph W Michalski Jörg Kleeff Sandra Rauser Roland M Schmid Bernhard Küster Axel Walch Jens T Siveke MALDI imaging mass spectrometry for in situ proteomic analysis of preneoplastic lesions in pancreatic cancer.
description	The identification of new biomarkers for preneoplastic pancreatic lesions (PanINs, IPMNs) and early pancreatic ductal adenocarcinoma (PDAC) is crucial due to the diseases high mortality rate upon late detection. To address this task we used the novel technique of matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) on genetically engineered mouse models (GEM) of pancreatic cancer. Various GEM were analyzed with MALDI IMS to investigate the peptide/protein-expression pattern of precursor lesions in comparison to normal pancreas and PDAC with cellular resolution. Statistical analysis revealed several discriminative m/z-species between normal and diseased tissue. Intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) could be distinguished from normal pancreatic tissue and PDAC by 26 significant m/z-species. Among these m/z-species, we identified Albumin and Thymosin-beta 4 by liquid chromatography and tandem mass spectrometry (LC-MS/MS), which were further validated by immunohistochemistry, western blot, quantitative RT-PCR and ELISA in both murine and human tissue. Thymosin-beta 4 was found significantly increased in sera of mice with PanIN lesions. Upregulated PanIN expression of Albumin was accompanied by increased expression of liver-restricted genes suggesting a hepatic transdifferentiation program of preneoplastic cells. In conclusion we show that GEM of endogenous PDAC are a suitable model system for MALDI-IMS and subsequent LC-MS/MS analysis, allowing in situ analysis of small precursor lesions and identification of differentially expressed peptides and proteins.
format	article
author	Barbara M Grüner Hannes Hahne Pawel K Mazur Marija Trajkovic-Arsic Stefan Maier Irene Esposito Evdokia Kalideris Christoph W Michalski Jörg Kleeff Sandra Rauser Roland M Schmid Bernhard Küster Axel Walch Jens T Siveke
author_facet	Barbara M Grüner Hannes Hahne Pawel K Mazur Marija Trajkovic-Arsic Stefan Maier Irene Esposito Evdokia Kalideris Christoph W Michalski Jörg Kleeff Sandra Rauser Roland M Schmid Bernhard Küster Axel Walch Jens T Siveke
author_sort	Barbara M Grüner
title	MALDI imaging mass spectrometry for in situ proteomic analysis of preneoplastic lesions in pancreatic cancer.
title_short	MALDI imaging mass spectrometry for in situ proteomic analysis of preneoplastic lesions in pancreatic cancer.
title_full	MALDI imaging mass spectrometry for in situ proteomic analysis of preneoplastic lesions in pancreatic cancer.
title_fullStr	MALDI imaging mass spectrometry for in situ proteomic analysis of preneoplastic lesions in pancreatic cancer.
title_full_unstemmed	MALDI imaging mass spectrometry for in situ proteomic analysis of preneoplastic lesions in pancreatic cancer.
title_sort	maldi imaging mass spectrometry for in situ proteomic analysis of preneoplastic lesions in pancreatic cancer.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/5384f88b088940dfbfa369db2094a494
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MALDI imaging mass spectrometry for in situ proteomic analysis of preneoplastic lesions in pancreatic cancer.

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