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Proteomics Clin Appl. 2015 Aug;9(7-8):651-61. doi: 10.1002/prca.201400194.

Identification of six cell surface proteins for specific liver targeting.

Author information

1
Translational Technologies and Bioinformatics, Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland.
2
Drug Disposition and Safety, Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland.
3
Translational Medicine - Infectious Diseases, Pharma Research and Early Development (pRED), Roche Innovation Center New York, New York, NY, USA.
4
External Alliances and Portfolio Management, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Shanghai, Pudong, Shanghai, P. R. China.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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 AND CLINICAL RELEVANCE:

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.

KEYWORDS:

Cell surface capture; Hydrazide chemistry; Liver; MS; N-glycoproteins

PMID:
26097162
DOI:
10.1002/prca.201400194
[Indexed for MEDLINE]

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