Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-63574
Boysen, Gunther; Bausch-Fluck, Damaris; Thoma, Claudio R; Nowicka, Anna M; Stiehl, Daniel P; Cima, Igor; Van-Duc, Luu; von Teichman, Adriana; Hermanns, Thomas; Sulser , Tullio; Ingold-Heppner, Barbara; Fankhauser, Niklaus; Wenger, Roland H; Krek, Wilhelm; Schraml, Peter; Wollscheid, Bernd; Moch, Holger (2012). Identification and Functional Characterization of pVHL-Dependent Cell Surface Proteins in Renal Cell Carcinoma. Neoplasia, 14(6):535-546.
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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research|
04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
04 Faculty of Medicine > University Hospital Zurich > Urological Clinic
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||19 Jul 2012 15:20|
|Last Modified:||21 Feb 2013 02:46|
|Funders:||UBS AG, Swiss National Cancer Foundation, Zurich Cancer League, National Center of Competence in Research Neural Plasticity and Repair|
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