Reference : Netrin-1 Mediates Early Events in Pancreatic Adenocarcinoma Progression, Acting on Tu...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Oncology
http://hdl.handle.net/2268/22733
Netrin-1 Mediates Early Events in Pancreatic Adenocarcinoma Progression, Acting on Tumor and Endothelial Cells.
English
Dumartin, L. [> > > >]
Quemener, C. [> > > >]
Laklai, H. [> > > >]
Herbert, J. [> > > >]
Bicknell, R. [> > > >]
Bousquet, C. [> > > >]
Pyronnet, S. [> > > >]
Castronovo, Vincenzo mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire - GIGA-R : Labo de recherche sur les métastases >]
Schilling, M. K. [> > > >]
Bikfalvi, A. [> > > >]
Hagedorn, M. [> > > >]
Apr-2010
Gastroenterology
W.B. Saunders
138
4
1595-606
Yes (verified by ORBi)
International
0016-5085
1528-0012
Philadelphia
PA
[en] Netrin-1 ; pancreatic ductal adenocarcinoma ; chick embryo ; invasion ; microarray ; endothelial cell ; angiogenesis ; apoptosis
[en] BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. It is characterized by substantial tumor cell invasion and early-stage metastasis. We developed an in vivo model to analyze interactions between cancer and stromal cells during early stages of PDAC. METHODS: Human pancreatic adenocarcinoma cells were grafted onto the chick chorioallantoic membrane (CAM). Human and chicken GeneChips were used simultaneously to study gene regulation during PDAC cell invasion. Bioinformatic analysis was used to identify human orthologs and cell specificity of gene expression. The effects of netrin-1 encoded by NTN1 were investigated in adhesion, invasion, and apoptosis assays. The effects of NTN1 silencing with small interfering RNAs were investigated in PDAC cells in vivo. NTN1 expression was measured in human PDAC samples. RESULTS: PDAC cells rapidly invade the CAM stroma and remodel the CAM vasculature. More than 870 stromal genes were up-regulated by >2-fold; the angiogenesis regulators vascular endothelial growth factor D, thrombospondin 1, and CD151 were among the most highly regulated genes. Silencing of tumor cell NTN1, which is up-regulated 4-fold in the PDAC model, inhibited tumor cell invasion in vivo. Netrin-1 conferred apoptosis resistance to tumor and endothelial cells in vitro, induced their invasion, and provided an adhesive substrate for tumor cells. NTN1 and its gene product are strongly overexpressed in human PDAC samples. CONCLUSIONS: We developed a useful tool to study the invasive mechanisms of early-stage PDAC. Netrin-1 might be an important regulator of pancreatic tumor growth that functions in tumor and endothelial cells.
GIGA-Cancer
Union Européenne = European Union - UE = EU (STROMA) ; Fondation pour la Rechercher Médicale and Ministère de la Recherche
http://hdl.handle.net/2268/22733
10.1053/j.gastro.2009.12.061
Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Restricted access
DUMARTIN L GASTROENTEROLOGY 2010.pdfPublisher postprint2.36 MBRequest copy

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.