| Identification and Functional Characterization of pVHL-Dependent Cell Surface Proteins in Renal Cell Carcinoma. | |
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MedLine Citation:
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PMID: 22806541 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: Neoplasia (New York, N.Y.) Volume: 14 ISSN: 1476-5586 ISO Abbreviation: Neoplasia Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-07-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100886622 Medline TA: Neoplasia Country: Canada |
Other Details:
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Languages: eng Pagination: 535-46 Citation Subset: IM |
Affiliation:
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Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. |
Export Citation:
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Descriptor/Qualifier:
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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