Systems Biology of Cancer Stem Cells
Cancer stem cells (CSCs) represent a very small subset of the tumor bulk with highly malignant properties. CSCs are responsible for tumor initiation, growth and metastasis, making them promising targets for innovative cancer therapies. In order to reveal molecular markers and determinants of CSCs, we employ highly metastatic pancreatic cancer cell lines. Pancreatic CSCs are enriched in three-dimensional spheroid cultures and compared to bulk tumor cells using wholistic omics-approaches such as proteomics (PTX) and transcriptomics (TCX). Using both technologies, 100-500 differentially expressed genes/proteins may be identified. Strict filtering according to occurrence in biological replicates and comparing with published genes and proteins known to have a role in cancer facilitates the identification of a hand full of candidate markers for subsequent functional validation. Our approach highlights the power of combining unbiased -omics setups with focused functional analyses for the identification of key regulators of CSCs, an approach that warrants further application to identify CSCs proteins amenable to drug targeting.
Wilmes A, Limonciel A, Aschauer L, Moenks K, Bielow C, Leonard MO, et al. Application of integrated transcriptomic, proteomic and metabolomic profiling for the delineation of mechanisms of drug induced cell stress. Journal of proteomics 2013;79:180-94.
Melchior K, Tholey A, Heisel S, Keller A, Lenhof H-P, Meese E, et al. Protein- versus peptide fractionation in the first dimension of two-dimensional high-performance liquid chromatography-matrix-assisted laser desorption/ionization tandem mass spectrometry for qualitative proteome analysis of tissue samples. Journal of Chromatography a 2010;1217:6159-68.
Melchior K, Tholey A, Heisel S, Keller A, Lenhof HP, Meese E, et al. Proteomic study of human glioblastoma multiforme tissue employing complementary two-dimensional liquid chromatography- and mass spectrometry-based approaches. Journal of proteome research 2009;8:4604-14.
Yoo C, Patwa TH, Kreunin P, Miller FR, Huber CG, Nesvizhskii AI, et al. Comprehensive analysis of proteins of pH fractionated samples using monolithic LC/MS/MS, intact MW measurement and MALDI-QIT-TOF MS. Journal of mass spectrometry : JMS 2007;42:312-34.
Yoo C, Zhao J, Pal M, Hersberger K, Huber CG, Simeone DM, et al. Automated integration of monolith-based protein separation with on-plate digestion for mass spectrometric analysis of esophageal adenocarcinoma human epithelial samples. Electrophoresis 2006;27:3643-51.
Christian Huber, PhD
Professor for Chemistry
Department of Biosciences
University of Salzburg
Systems Biology Approaches to Understand Cancer Stem Cells (CSC) and their environment
Combined Proteomics and Transcriptomics identify genes and proteins specifically expressed in CSC and non-CSC. Subsequent functional analysis reveal molecular determinants of CSC and putative drug targets for innovative future therapies.