Document Detail

Identification and functional characterization of pVHL-dependent cell surface proteins in renal cell carcinoma.
MedLine Citation:
PMID:  22806541     Owner:  NLM     Status:  MEDLINE    
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.
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    
Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
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MeSH Terms
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism
Carcinoma, Renal Cell / genetics,  metabolism*
Cell Line
Gene Expression Regulation, Neoplastic
Glycoproteins / genetics,  metabolism
Kidney Neoplasms / genetics,  metabolism*
Membrane Proteins / genetics,  metabolism*
Neprilysin / blood,  genetics,  metabolism
Reproducibility of Results
Von Hippel-Lindau Tumor Suppressor Protein / metabolism*
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Glycoproteins; 0/Membrane Proteins; EC; EC protein, human; EC Hippel-Lindau Tumor Suppressor Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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