title: Identification of six cell surface proteins for specific liver targeting.
abstract: OBJECTIVE
  Cell surface proteins are the primary means for a cell to sense and interact with its environment and their dysregulation has been linked to numerous diseases. In particular, the identification of proteins specific to a single tissue type or to a given disease phenotype may enable the characterization of novel therapeutic targets. We tested here the feasibility of a cell surface proteomics approach to identify pertinent markers directly in a clinically relevant tissue.
  
  
  METHODS
  We analyzed the cell surface proteome of freshly isolated primary heptatocytes using a glycocapture-specific approach combined with a robust bioinformatics filtering.
  
  
  RESULTS
  Using primary lung epithelial cell cultures as negative controls, we identified 32 hepatocyte-specific cell surface proteins candidates. We used mRNA expression to select six markers that may provide adequate specificity for targeting therapeutics to the liver.
  
  
  CONCLUSIONS
  We demonstrate the feasibility and the importance of conducting such studies directly in a clinically relevant tissue. In particular, the cell surface proteome of freshly isolated hepatocytes differed substantially from cultured cell lines.
authors.affiliation: Translational Technologies and Bioinformatics, Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Axel
authors.initials: A
authors.lastname: Ducret
authors.affiliation: Translational Technologies and Bioinformatics, Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kux van Geijtenbeek
authors.affiliation: Translational Technologies and Bioinformatics, Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Röder
authors.affiliation: Drug Disposition and Safety, Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Simon
authors.affiliation: Translational Technologies and Bioinformatics, Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chin
authors.affiliation: Translational Technologies and Bioinformatics, Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Berrera
authors.affiliation: Translational Medicine - Infectious Diseases, Pharma Research and Early Development (pRED), Roche Innovation Center New York, New York, NY, USA.
authors.forename: Lore
authors.initials: L
authors.lastname: Gruenbaum
authors.affiliation: External Alliances and Portfolio Management, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Shanghai, Pudong, Shanghai, P. R. China.
authors.forename: Changhua
authors.initials: C
authors.lastname: Ji
authors.affiliation: Translational Technologies and Bioinformatics, Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Cutler
mesh_terms: D016503:Drug Delivery Systems; D054794:Glycomics; D006023:Glycoproteins / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009928:Organ Specificity; D010455:Peptides / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D006023:Glycoproteins; D008565:Membrane Proteins; D010455:Peptides; D020543:Proteome
keywords: Cell surface capture; Hydrazide chemistry; Liver; MS; N-glycoproteins