Proteomic surfaceome analysis of mesothelioma

Ziegler, Annemarie; Cerciello, Ferdinando; Bigosch, Colette; Bausch-Fluck, Damaris; Felley-Bosco, Emanuela; Ossola, Reto; Soltermann, Alex; Stahel, Rolf A.; Wollscheid, Bernd

doi:10.1016/j.lungcan.2011.07.009

« Previous Next »Lung Cancer
Volume 75, Issue 2 , Pages 189-196, February 2012

Proteomic surfaceome analysis of mesothelioma

Annemarie Ziegler
- Clinic of Oncology, University Hospital Zürich, 8044 Zürich, Switzerland
- These authors contributed equally to this work.
- Present address: Centro de Genética Humana, Clínica Alemana-Universidad del, Desarrollo, Santiago, Chile.
Ferdinando Cerciello
- Clinic of Oncology, University Hospital Zürich, 8044 Zürich, Switzerland
- Institute of Molecular Systems Biology, Swiss Federal Institute of Technology (ETH), 8093 Zürich, Switzerland
- These authors contributed equally to this work.
- Corresponding author at: ETH Zürich, Institute of Molecular Systems Biology (IMSB), HPT E52, Wolfgang-Pauli-Strasse 16, CH-8093, Zürich, Switzerland. Tel.: +41 44 633 68 56; fax: +41 44 633 10 51.
Colette Bigosch
- Clinic of Oncology, University Hospital Zürich, 8044 Zürich, Switzerland
- Present address: Umweltmikrobiologie, EAWAG, Dübendorf, Switzerland.
Damaris Bausch-Fluck
- Institute of Molecular Systems Biology, Swiss Federal Institute of Technology (ETH), 8093 Zürich, Switzerland
Emanuela Felley-Bosco
- Clinic of Oncology, University Hospital Zürich, 8044 Zürich, Switzerland
Reto Ossola
- Institute of Molecular Systems Biology, Swiss Federal Institute of Technology (ETH), 8093 Zürich, Switzerland
Alex Soltermann
- Institute for Surgical Pathology, University Hospital Zürich, 8044 Zürich, Switzerland
Rolf A. Stahel
- Clinic of Oncology, University Hospital Zürich, 8044 Zürich, Switzerland
Bernd Wollscheid
- Institute of Molecular Systems Biology, Swiss Federal Institute of Technology (ETH), 8093 Zürich, Switzerland
- Corresponding author at: ETH Zürich, Institute of Molecular Systems Biology (IMSB), HPT D77, Wolfgang-Pauli-Strasse 16, CH-8093, Zürich, Switzerland. Tel.: +41 44 633 36 84; fax: +41 44 633 10 51.

Received 10 February 2011; received in revised form 27 April 2011; accepted 13 July 2011. published online 11 August 2011.

Abstract

Identification of new markers for malignant pleural mesothelioma (MPM) is a challenging clinical need. Here, we propose a quantitative proteomics primary screen of the cell surface exposed MPM N-glycoproteins, which provides the basis for the development of new protein-based diagnostic assays. Using the antibody-independent mass-spectrometry based cell surface capturing (CSC) technology, we specifically investigated the N-glycosylated surfaceome of MPM towards the identification of protein-marker candidates discriminatory between MPM and lung adenocarcinoma (ADCA). Relative quantitative CSC analysis of MPM cell line ZL55 in comparison with ADCA cell line Calu-3 revealed a bird's eye view of their respective surfaceomes. In a secondary screen of fifteen MPM and six ADCA, we used high throughput low density microarrays (LDAs) to verify specificity and sensitivity of nineteen N-glycoproteins overregulated in the surfaceome of MPM. This proteo-transcriptomic approach revealed thy-1/CD90 (THY1) and teneurin-2 (ODZ2) as protein-marker candidates for the discrimination of MPM from ADCA. Thy-1/CD90 was further validated by immunohistochemistry on frozen tissue sections of MPM and ADCA samples. Together, we present a combined proteomic and transcriptomic approach enabling the relative quantitative identification and pre-clinical selection of new MPM marker candidates.

Keywords: Mesothelioma, Surfaceome, Cell surface capturing (CSC) technology, N-glycoproteins, Surface markers, CD90, ODZ2