[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.
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]
Bi X, Lin Q, Foo TW, Joshi S, You T, Shen HM, Ong CN, Cheah PY, Eu KW, Hew CL. Proteomic analysis of colorectal cancer reveals alterations in metabolic pathways: mechanism of tumorigenesis. Mol Cell Proteomics 2006;5:1119-30.
Dukes CE. The classification of cancer of the rectum. J Pathol Bacteriol 1932;35:323-32.
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL. Genetic alterations during colorectal-tumor development. N Engl J Med 1988;319:525-32.
Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nat Rev Genet 2006;7:21-33.
Davies RJ, Miller R, Coleman N. Colorectal cancer screening: prospects for molecular stool analysis. Nat Rev Cancer 2005;5:199-209.
Parsons DW, Wang TL, Samuels Y, Bardelli A, Cummins JM, DeLong L, Silliman N, Ptak J, Szabo S, Willson JK, Markowitz S, Kinzler KW, et al. Colorectal cancer: mutations in a signalling pathway. Nature 2005;436:792.
Polley AC, Mulholland F, Pin C, Williams EA, Bradburn DM, Mills SJ, Mathers JC, Johnson IT. Proteomic analysis reveals field-wide changes in protein expression in the morphologically normal mucosa of patients with colorectal neoplasia. Cancer Res 2006;66:6553-62.
Pelegrin A, Folli S, Buchegger F, Mach JP, Wagnieres G, van den Bergh H. Antibody-fluorescein conjugates for photoimmunodiagnosis of human colon carcinoma in nude mice. Cancer 1991;67:2529-37.
Folli S, Wagnieres G, Pelegrin A, Calmes JM, Braichotte D, Buchegger F, Chalandon Y, Hardman N, Heusser C, Givel JC. Immunophotodiagnosis of colon carcinomas in patients injected with fluoresceinated chimeric antibodies against carcinoembryonic antigen. Proc Natl Acad Sci USA 1992;89:7973-7.
Martin MJ. Current stage-specific chemotherapeutic options in colon cancer. Expert Rev Anticancer Ther 2005;5:695-704.
Goyle S, Maraveyas A. Chemotherapy for colorectal cancer. Dig Surg 2005;22:401-14.
Arsene D, Galais MP, Bouhier-Leporrier K, Reimund JM. Recent developments in colorectal cancer treatment by monoclonal antibodies. Expert Opin Biol Ther 2006;6:1175-92.
Carter PJ. Potent antibody therapeutics by design. Nat Rev Immunol 2006;6:343-57.
Schrama D, Reisfeld RA, Becker JC. Antibody targeted drugs as cancer therapeutics. Nat Rev Drug Discov 2006;5:147-59.
Ying-Tao Z, Yi-Ping G, Lu-Sheng S, Yi-Li W. Proteomic analysis of differentially expressed proteins between metastatic and non-metastatic human colorectal carcinoma cell lines. Eur J Gastroenterol Hepatol 2005;17:725-32.
Alfonso P, Nunez A, Madoz-Gurpide J, Lombardia L, Sanchez L, Casal JI. Proteomic expression analysis of colorectal cancer by two-dimensional differential gel electrophoresis. Proteomics 2005;5:2602-11.
Rybak JN, Ettorre A, Kaissling B, Giavazzi R, Neri D, Elia G. In vivo protein biotinylation for identification of organ-specific antigens accessible from the vasculature. Nat Methods 2005;2:291-8.
Castronovo V, Waltregny D, Kischel P, Roesli C, Elia G, Rybak JN, Neri D. A chemical proteomics approach for the identification of accessible antigens expressed in human kidney cancer. Mol Cell Proteomics 2006;5:2083-91.
Castronovo V, Kischel P, Guillonneau F, de Leval L, Deféchereux T, De Pauw E, Neri D, Waltregny D. Identification of specific reachable molecular targets in human breast cancer using a versatile ex vivo proteomic method. Proteomics 2007;7:1188-96.
Scheurer SB, Roesli C, Neri D, Elia G. A comparison of different biotinylation reagents, tryptic digestion procedures, and mass spectrometric techniques for 2-D peptide mapping of membrane proteins. Proteomics 2005;5:3035-9.
Silacci M, Brack S, Schirru G, Mårlind J, Ettorre A, Merlo A, Viti F, Neri D. Design, construction, and characterization of a large synthetic human antibody phage display library. Proteomics 2005;5:2340-50.
Brack SS, Silacci M, Birchler M, Neri D. Tumor-targeting properties of novel antibodies specific to the large isoform of tenascin-C. Clin Cancer Res 2006;12:3200-8.
Viti F, Nilsson F, Demartis S, Huber A, Neri D. Design and use of phage display libraries for the selection of antibodies and enzymes. Methods Enzymol 2000;326:480-505.
Dentler WL. Nonradioactive methods for labeling and identifying membrane surface proteins. Methods Cell Biol 1995;47:407-11.
Zhang J, Liu WL, Tang DC, Chen L, Wang M, Pack SD, Zhuang Z, Rodgers GP. Identification and characterization of a novel member of olfactomedin-related protein family, hGC-1, expressed during myeloid lineage development. Gene 2002;283:83-93.
Zhang X, Huang Q, Yang Z, Li Y, Li CY. GW112, a novel antiapoptotic protein that promotes tumor growth. Cancer Res 2004;64:2474-81.
Koshida S, Kobayashi D, Moriai R, Tsuji N, Watanabe N. Specific overexpression of OLFM4 (GW112/HGC-1) mRNA in colon, breast and lung cancer tissues detected using quantitative analysis. Cancer Sci 2007;98:315-20.
Liu W, Zhu J, Cao L, Rodgers JP. Expression of hGC-1 is correlated with differentiation of gastric carcinoma. Histopathology 2007;51:157-65.
Winter G, Griffiths AD, Hawkins RE, Hoogenboom HR. Making antibodies by phage display technology. Annu Rev Immunol 1994;12:433-55.
Neri D, Bicknell R. Tumour vascular targeting. Nat Rev Cancer 2005;5:436-46.
Wu AM, Senter PD. Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol 2005;23:1137-46.
Sharkey RM, Goldenberg DM. Targeted therapy of cancer: new prospects for antibodies and immunoconjugates. CA Cancer J Clin 2006;56:226-43.
Ricart AD, Tolcher AW. Technology insight: cytotoxic drug immunoconjugates for cancer therapy. Nat Clin Pract Oncol 2007;4:245-55.
Pham CT. Neutrophil serine proteases: specific regulators of inflammation. Nat Rev Immunol 2006;6:541-50.
Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 2005;7:211-17.
Colombatti A, Doliana R, Bot S, Canton A, Mongiat M, Mungiguerra G, Paron-Cilli S, Spessotto P. The EMILIN protein family. Matrix Biol 2000;19:289-301.
Zacchigna L, Vecchione C, Notte A, Cordenonsi M, Dupont S, Maretto S, Cifelli G, Ferrari A, Maffei A, Fabbro C, Braghetta P, Marino G, et al. Emilin1 links TGF-β maturation to blood pressure homeostasis. Cell 2006;124:929-42.
Friedl A, Stoesz SP, Buckley P, Gould MN. Neutrophil gelatinase- associated lipocalin in normal and neoplastic human tissues. Cell type-specific pattern of expression. Histochem J 1999;31:433-41.
Bauer M, Eickhoff JC, Gould MN, Mundhenke C, Maass N, Friedl A. Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of poor prognosis in human primary breast cancer. Breast Cancer Res Treat 2008;108:389-97.
Lim R, Ahmed N, Borregaard N Riley C, Wafai R, Thompson EW, Quinn MA, Rice GE. Neutrophil gelatinase-associated lipocalin (NGAL) an early-screening biomarker for ovarian cancer: NGAL is associated with epidermal growth factor-induced epithelio-mesenchymal transition. Int J Cancer 2007;120:2426-34.
Fang WK, Xu LY, Lu XF, Liao LD, Cai WJ, Shen ZY, Li EM. A novel alternative spliced variant of neutrophil gelatinase-associated lipocalin receptor in oesophageal carcinoma cells. Biochem J 2007;403:297-303.
Oue N, Aung PP, Mitani Y, Kuniyasu H, Nakayama H, Yasui W. Genes involved in invasion and metastasis of gastric cancer identified by array-based hybridization and serial analysis of gene expression. Oncology 2005;69:17-22.
Kaspar M, Trachsel E, Neri D. The antibody-mediated targeted delivery of interleukin-15 and GM-CSF to the tumor neovasculature inhibits tumor growth and metastasis. Cancer Res 2007;67:4940-8.
Riechmann L, Clark M, Waldmann H, Winter G. Reshaping human antibodies for therapy. Nature 1988;332:323-7.