Article (Scientific journals)
Identification of new accessible tumor antigens in human colon cancer by ex vivo protein biotinylation and comparative mass spectrometry analysis.
Conrotto, Paolo; Roesli, Cristof; Rybak, Jascha et al.
2008In International Journal of Cancer, 123 (12), p. 2856-2864
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Keywords :
colorectal cancer; proteomics; biomarkers; tumor targeting; immunotherapy
Abstract :
[en] One of the most promising new strategies for the development of efficacious cancer therapies relies on the targeted delivery of biopharmaceutical to the tumor environment by the use of selective and specific antibodies. The identification of accessible perivascular proteins selectively overexpressed in cancer tissue may facilitate the development of antibody-based biopharmaceutical administration. This approach is potentially highly selective and specific, combining the presence of tumor biomarkers readily accessible from the blood vessels and the high rate of angiogenesis characteristic of cancer tissues. We performed ex vivo perfusions of surgically resected human colon cancer using a reactive ester derivative of biotin, thus achieving a selective covalent modification of accessible proteins in vascular structures and stroma. After extraction and purification, biotinylated proteins were digested and the resulting peptides submitted to a comparative mass spectrometry-based proteomic analysis, revealing quantitative differences between normal and cancer colon. Sixty-seven of the total 367 proteins identified were found to be preferentially expressed at the tumor site. We generated human monoclonal antibodies against 2 potential tumor targets, NGAL and GW112, and we proved their selective expression in cancer colon and not or barely in healthy tissues. This article presents the first proteomic analysis of human colorectal cancer structures readily accessible from the tumor vasculature, revealing the overexpression of novel tumor antigens which may serve as selective targets for antibody-based imaging and therapeutic biomolecular strategies. (c) 2008 Wiley-Liss, Inc.
Research center :
Giga-Cancer - ULiège
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Biotechnology
Oncology
Author, co-author :
Conrotto, Paolo
Roesli, Cristof
Rybak, Jascha
Kischel, Philippe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Labo de recherche sur les métastases
Waltregny, David  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Labo de recherche sur les métastases - Département des sciences biomédicales et précliniques
Neri, Dario
Castronovo, Vincenzo ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire - Labo de recherche sur les métastases
Language :
English
Title :
Identification of new accessible tumor antigens in human colon cancer by ex vivo protein biotinylation and comparative mass spectrometry analysis.
Publication date :
2008
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
Wiley Liss, Inc., New York, United States - New York
Volume :
123
Issue :
12
Pages :
2856-2864
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
EU projects STROMA
Funders :
SNSF - Swiss National Science Foundation [CH]
Gebert Rüf Foundation [CH]
SKL - Schweizerische Krebsliga [CH]
ETH Zürich - Eidgenössische Technische Hochschule Zürich [CH]
EU - European Union [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Télévie [BE]
CAC - Centre anticancéreux près l'Université de Liège asbl [BE]
UICC - Union for International Cancer Control [CH]
Funding text :
FLUORMMPI; IMMUNOPDT
Available on ORBi :
since 25 January 2009

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