Pleiotrophin, a candidate gene for poor tumor vasculature and in vivo neuroblastoma sensitivity to irinotecan

Détails

ID Serval
serval:BIB_B2034381050E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Pleiotrophin, a candidate gene for poor tumor vasculature and in vivo neuroblastoma sensitivity to irinotecan
Périodique
Oncogene
Auteur(s)
Calvet  L., Geoerger  B., Regairaz  M., Opolon  P., Machet  L., Morizet  J., Joseph  J. M., Elie  N., Vassal  G.
ISSN
0950-9232 (Print)
Statut éditorial
Publié
Date de publication
05/2006
Volume
25
Numéro
22
Pages
3150-9
Notes
Comparative Study
Journal Article --- Old month value: May 25
Résumé
In vivo neuroblastoma (NB) xenograft model, resistant to the DNA-topoisomerase I inhibitor irinotecan (CPT-11), has been established to study resistance mechanisms acquired in a therapeutic setting. Common mechanisms of resistance were not involved in this resistance. Thus, we compared the gene expression profiles of sensitive, resistant, and reverted tumors using cDNA expression arrays. Expression of selected transcripts was confirmed by quantitative real-time PCR. We found that pleiotrophin (PTN), a heparin-binding growth factor, was the only gene significantly affected: PTN gene expression was downregulated in all resistant tumors (8-14-fold) as compared to sensitive tumors, and was increased (2-4-fold) in all reverted tumors as compared to resistant tumors. PTN thus appeared to be a likely candidate gene associated with resistance to CPT-11 in this in vivo model. To investigate the direct implication of PTN in NB, we transfected two NB cell lines with RNA interferences in order to silence PTN. PTN failed to demonstrate implication in resistance to CPT-11 in vitro but could influence sensitivity to CPT-11 exclusively through an in vivo mechanism. Indeed, vasculature was significantly enhanced in resistant NB xenografts compared to sensitive and reverted xenografts, and we suggest that PTN is acting in our resistant in vivo NB model as an angiostatic factor.
Mots-clé
Animals Camptothecin/*analogs & derivatives/therapeutic use Carrier Proteins/antagonists & inhibitors/*genetics Child, Preschool Cytokines/antagonists & inhibitors/*genetics DNA Topoisomerases, Type I/antagonists & inhibitors *Drug Resistance, Neoplasm Gene Expression Profiling Gene Expression Regulation Humans Male Mice Neovascularization, Pathologic/*etiology Neuroblastoma/blood supply/*drug therapy/genetics Oligonucleotide Array Sequence Analysis RNA, Messenger/metabolism RNA, Small Interfering/pharmacology Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured Xenograft Model Antitumor Assays
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 9:07
Dernière modification de la notice
20/08/2019 15:20
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