[en] Pancreas ductal adenocarcinoma (PDAC) remains a deadly malignancy with poor early diagnostic and no effective therapy. Although several proteomic studies have performed comparative analysis between normal and malignant tissues, there is a lack of clear characterization of proteins that could be of clinical value. Systemically reachable ("potentially accessible") proteins, suitable for imaging technologies and targeted therapies represent a major group of interest. The current study explores potentially accessible proteins overexpressed in PDAC, employing innovative proteomics technologies. In the discovery phase, potentially accessible proteins from fresh human normal and PDAC tissues were ex vivo biotinylated, isolated and identified using 2D-nano-HPLC-MS/MS method. The analysis revealed 422 up-regulated proteins in the tumor, of which 83 (including protein isoforms) were evaluated as potentially accessible. Eleven selected candidates were further confirmed as up-regulated using Western blot and multiple reaction monitoring protein quantification. Of these, transforming growth factor beta-induced (TGFBI), latent transforming growth factor beta binding 2 (LTBP2), and asporin (ASPN) were further investigated by employing large scale immunohistochemistry-based validations. They were found to be significantly expressed in a large group of clinical PDAC samples compared to corresponding normal and inflammatory tissues. In conclusion, TGFBI, LTBP2, and ASPN are novel, overexpressed, and potentially accessible proteins in human PDAC. They bear the potential to be of clinical value for diagnostic and therapeutic applications and merit further studies using in vivo models.
Research Center/Unit :
Giga-Cancer - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Turtoi, Andrei ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Musmeci, Davide; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Wang, Yinghong; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Dumont, Bruno ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Somja, Joan ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Bevilacqua, Generoso; University Hospital of Pisa, Italy > Division of Surgical, Molecular and Ultrastructural Pathology
De Pauw, Edwin ; Université de Liège - ULiège > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.)
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Language :
English
Title :
Identification of novel accessible proteins bearing diagnostic and therapeutic potential in human pancreatic ductal adenocarcinoma
Publication date :
02 September 2011
Journal title :
Journal of Proteome Research
ISSN :
1535-3893
eISSN :
1535-3907
Publisher :
American Chemical Society, Washington, United States - District of Columbia
Volume :
10
Issue :
9
Pages :
4302-13
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
FP7 - 201342 - ADAMANT - ANTIBODY DERIVATIVES AS MOLECULAR AGENTS FOR NEOPLASTIC TARGETING
Funders :
ULg - University of Liège [BE] CE - Commission Européenne [BE] F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] Télévie [BE]
Funding text :
This work was supported by a grant from the Research Concerted
Action (IDEA project) of the University of Li!ege (ULG),
Belgium, from the CEE (FP7 network: ADAMANT-Antibody
Derivatives As Molecular Agents for Neoplastic Targeting
(HEALTH-F2!2007!201342)), from the National Fund for
Scientic Research (NFSR, Belgium) and TELEVIE as well as from
the Centre Anti-Cancereux of the ULG. We acknowledge the
support of GIGA-Proteomics Platform of theULG for experimental
support and are particularly thankful to Pascale Heneaux for IHC
experiments.
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