Document Detail


Identification and functional characterization of pVHL-dependent cell surface proteins in renal cell carcinoma.
MedLine Citation:
PMID:  22806541     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The identification of cell surface accessible biomarkers enabling diagnosis, disease monitoring, and treatment of renal cell carcinoma (RCC) is as challenging as the biology and progression of RCC is unpredictable. A hallmark of most RCC is the loss-of-function of the von Hippel-Lindau (pVHL) protein by mutation of its gene (VHL). Using the cell surface capturing (CSC) technology, we screened and identified cell surface N-glycoproteins in pVHL-negative and positive 786-O cells. One hundred six cell surface N-glycoproteins were identified. Stable isotope labeling with amino acids in cell culture-based quantification of the CSC screen revealed 23 N-glycoproteins whose abundance seemed to change in a pVHL-dependent manner. Targeted validation experiments using transcriptional profiling of primary RCC samples revealed that nine glycoproteins, including CD10 and AXL, could be directly linked to pVHL-mediated transcriptional regulation. Subsequent human tumor tissue analysis of these cell surface candidate markers showed a correlation between epithelial AXL expression and aggressive tumor phenotype, indicating that pVHL-dependent regulation of glycoproteins may influence the biologic behavior of RCC. Functional characterization of the metalloprotease CD10 in cell invasion assays demonstrated a diminished penetrating behavior of pVHL-negative 786-O cells on treatment with the CD10-specific inhibitor thiorphan. Our proteomic surfaceome screening approach in combination with transcriptional profiling and functional validation suggests pVHL-dependent cell surface glycoproteins as potential diagnostic markers for therapeutic targeting and RCC patient monitoring.
Authors:
Gunther Boysen; Damaris Bausch-Fluck; Claudio R Thoma; Anna M Nowicka; Daniel P Stiehl; Igor Cima; Van-Duc Luu; Adriana von Teichman; Thomas Hermanns; Tullio Sulser; Barbara Ingold-Heppner; Niklaus Fankhauser; Roland H Wenger; Wilhelm Krek; Peter Schraml; Bernd Wollscheid; Holger Moch
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  14     ISSN:  1476-5586     ISO Abbreviation:  Neoplasia     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-07-18     Completed Date:  2012-11-13     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  535-46     Citation Subset:  IM    
Affiliation:
Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism
Carcinoma, Renal Cell / genetics,  metabolism*
Cell Line
Gene Expression Regulation, Neoplastic
Glycoproteins / genetics,  metabolism
Humans
Kidney Neoplasms / genetics,  metabolism*
Membrane Proteins / genetics,  metabolism*
Neprilysin / blood,  genetics,  metabolism
Proteomics
Reproducibility of Results
Von Hippel-Lindau Tumor Suppressor Protein / metabolism*
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Glycoproteins; 0/Membrane Proteins; EC 3.4.24.11/Neprilysin; EC 6.3.2.19/VHL protein, human; EC 6.3.2.19/Von Hippel-Lindau Tumor Suppressor Protein
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