AG Schwamborn – Mass Spectrometry Imaging (MSI)

Team: 
PD Dr. med. Dr. nat. med. Kristina Schwamborn
Dr. rer. nat. Juliana Goncalves
Dr. med. Christine Bollwein

 

New and innovative technologies are needed to meet the challenges in modern pathology: continuous increase in complexity, extensiveness of diagnostic pathology work-up, limited tissue material, time to reach an accurate diagnosis, and costs. Personalized medicine and patient stratification call for tumor subtyping beyond classical histomorphology. As the proteome is much more complex and dynamic than the genome it presents a sensitive and specific probe of a cells and bodies function/ dysfunction. Thus, its analysis holds out the prospect of overcoming some of the limitations of other approaches in the identification of new disease marker molecules.

Many different platform technologies allow high throughput and high sensitivity investigations of the proteome, among them mass spectrometry (MS). It is a versatile and powerful tool for the analysis of proteins and peptides as well as other biological compounds such as DNA segments, lipids, metabolites, and other small molecules However, classical proteomic technologies require the sample to be in solution, thus, destroying tissue integrity and any information that could gained on histomorphology such as cell distribution and distance between cells. Additionally, in order to obtain pure cell populations, tissue samples have to be microdissected. This is not only a time-consuming step but also might lead to sample loss due to incomplete homogenization. Also, for a multitude of research questions (such as defining the proteome of scattered inflammatory or tumor cells in a stromal background) tissue microdissection even with the most advanced technologies is not really applicable in real life. Herein lie some of the advantages of matrix assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI), a method first described by Richard M. Caprioli in 1997. Intact tissue sections can be used to measure the relative abundance and spatial distribution of proteins, peptides, lipids, metabolites, and xenobiotics. Results can be visualized throughout a tissue section and correlated with histology (Figure 1). Latest advancements allow to measure small groups of cells and even single cells. As no target specific reagents such as antibodies are required the method is ideally suited to uncover new biomarkers.

 

 

Our group is in particular focused on the characterization of tumor tissues in order to aid in diagnosis and discover new markers for tumor subtyping by combining mass spectrometry imaging with histological annotation, and statistical analysis.

 

Collaborations:

  • Prof. Ron Heeren, M4i - Maastricht Multimodal Molecular Institute, Maastricht University, Niederlande
  • Prof. Richard M. Caprioli, Mass Spectrometry Research Center Vanderbilt University School of Medicine, Nashville, TN, USA
  • Prof. Peggi M. Angel, Cell and Molecular Pharmacology and Experimental Therapeutics, College of Medicine, Medical University of South Carolina, Charleston, SC, USA
  • Dr. Rita Casadonte, Proteopath, Tier
  • PD. Dr. Mark Kriegsmann, Institut für Pathologie, Universitätsklinikum Heidelberg
  • CEP
  • INTEGRATE-TN (Deutsche Krebshilfe)

Relevant Publications

Gonçalves JPL, Bollwein C, Schlitter AM, Martin B, Märkl B, Utpatel K, Weichert W, Schwamborn K. The Impact of Histological Annotations for Accurate Tissue Classification Using Mass Spectrometry Imaging. Metabolites. 2021 Oct 30;11(11):752. doi: 10.3390/metabo11110752. PMID: 34822410 

Lopes Gonçalves JP, Bollwein C, Weichert W, Schwamborn K. Implementation of Mass Spectrometry Imaging in Pathology: Advances and Challenges. Clin Lab Med. 2021 Jun;41(2):173-184. doi: 10.1016/j.cll.2021.03.001. PMID: 34020758 Review.

Martin B, Gonçalves JPL, Bollwein C, Sommer F, Schenkirsch G, Jacob A, Seibert A, Weichert W, Märkl B, Schwamborn K. A Mass Spectrometry Imaging Based Approach for Prognosis Prediction in UICC Stage I/II Colon Cancer. Cancers (Basel). 2021 Oct 26;13(21):5371. doi: 10.3390/cancers13215371. PMID: 34771536

Kriegsmann M, Zgorzelski C, Casadonte R, Schwamborn K, Muley T, Winter H, Eichhorn M, Eichhorn F, Warth A, Deininger SO, Christopoulos P, Thomas M, Longerich T, Stenzinger A, Weichert W, Müller-Tidow C, Kriegsmann J, Schirmacher P, Kriegsmann K. Mass Spectrometry Imaging for Reliable and Fast Classification of Non-Small Cell Lung Cancer Subtypes. Cancers (Basel). 2020 Sep 21;12(9):E2704. PMID: 32967325

Schwamborn K, Weirich G, Steiger K, Zimmermann G, Schmidmayr M, Weichert W, Caprioli RM. Discerning the Primary Carcinoma in Malignant Peritoneal and Pleural Effusions Using Imaging Mass Spectrometry-A Feasibility Study. Proteomics Clin Appl. 2019 Jan;13(1):e1800064. PMID: 30311431

Angel PM, Schwamborn K, Comte-Walters S, Clift CL, Ball LE, Mehta AS, Drake RR. Extracellular Matrix Imaging of Breast Tissue Pathologies by MALDI-Imaging Mass Spectrometry. Proteomics Clin Appl. 2019 Jan;13(1):e1700152. PMID: 30251340

Ly A, Longuespée R, Casadonte R, Wandernoth P, Schwamborn K, Bollwein C, Marsching C, Kriegsmann K, Hopf C, Weichert W, Kriegsmann J, Schirmacher P, Kriegsmann M, Deininger SO. Site-to-Site Reproducibility and Spatial Resolution in MALDI-MSI of Peptides from Formalin-Fixed Paraffin-Embedded Samples. Proteomics Clin Appl. 2019 Jan;13(1):e1800029. doi: 10.1002/prca.201800029. PMID: 30408343

Leung F, Eberlin LS, Schwamborn K, Heeren RMA, Winograd N, Cooks RG. Mass Spectrometry-Based Tissue Imaging: The Next Frontier in Clinical Diagnostics? Clin Chem. 2019 Apr;65(4):510-513. PMID: 30737204

Spraggins JM, Schwamborn K, Heeren RMA, Eberlin LS. The Importance of Clinical Tissue Imaging. Clin Mass Spectrom. 2019 Apr;12:47-49. PMID: 32483555

Porta Siegel T, Hamm G, Bunch J, Cappell J, Fletcher JS, Schwamborn K. Mass Spectrometry Imaging and Integration with Other Imaging Modalities for Greater Molecular Understanding of Biological Tissues. Mol Imaging Biol. 2018 Dec;20(6):888-901. PMID: 30167993

Schwamborn K, Kriegsmann M, Weichert W. MALDI imaging mass spectrometry – From bench to bedside. Biochim Biophys Acta. 2017 Jul;1865(7):776-783. PMID: 27810414

Schwamborn K. The Importance of Histology and Pathology in Mass Spectrometry Imaging. Adv Cancer Res. 2017;134:1-26. PMID: 28110647

Kriegsmann M, Casadonte R, Kriegsmann J, Dienemann H, Schirmacher P, Kobarg JH, Schwamborn K, Stenzinger A, Warth A, Weichert W. Reliable entity subtyping in Non-small cell Lung Cancer by MALDI Imaging Mass Spectrometry on Formalin-fixed Paraffin-embedded Tissue Specimens. Mol Cell Proteomics. 2016 Oct;15(10):3081-3089. PMID: 27473201

Schwamborn K, Caprioli RM. Molecular imaging by mass spectrometry — looking beyond classical histology. Nat Rev Cancer. 2010 Sep;10(9):639-46. PMID: 20720571

Schwamborn K, Caprioli RM. MALDI imaging mass spectrometry – painting molecular pictures. Mol Oncol. 2010 Dec; 4(6):529-38. PMID: 20965799

Schwamborn K. Imaging mass spectrometry in biomarker discovery and validation. J Proteomics. 2012 Aug 30;75(16):4990-8. PMID: 22749859