The NFL-TBS.40-63 anti-glioblastoma peptide enters selectively in glioma cells by endocytosis

TitreThe NFL-TBS.40-63 anti-glioblastoma peptide enters selectively in glioma cells by endocytosis
Type de publicationArticle de revue
AuteurLépinoux-Chambaud, Claire , Eyer, Joël
EditeurElsevier
TypeArticle scientifique dans une revue à comité de lecture
Année2013
LangueAnglais
Date2013/10/01
Numéro2
Pagination738 - 747
Volume454
Titre de la revueInternational Journal of Pharmaceutics
ISSN0378-5173
Mots-clésEndocytosis, Glioblastoma, Peptide, Tyrosine kinase receptor, Uptake
Résumé en anglais

Glioblastoma are the most frequent and aggressive tumour of the nervous system despite surgical resection associated with chemotherapy and radiotherapy. Recently, we showed that the NFL-TBS.40-63 peptide corresponding to the sequence of a tubulin-binding site of neurofilaments, enters selectively in glioblastoma cells where it blocks microtubule polymerization, inhibits their proliferation, and reduces tumour development in rats bearing glioblastoma (Bocquet et al., 2009; Berges et al., 2012a). Here, we characterized the molecular mechanism responsible for the uptake of NFL-TBS.40-63 peptide by glioblastoma cells. Unlike other cell penetrating peptides (CPPs), which use a balance between endocytosis and direct translocation, the NFL-TBS.40-63 peptide is unable to translocate directly through the membrane when incubated with giant plasma membrane vesicles. Then, using a panel of markers and inhibitors, flow cytometry and confocal microscopy investigations showed that the uptake occurs mainly through endocytosis. Moreover, glycosaminoglycans and αVβ3 integrins are not involved in the NFL-TBS.40-63 peptide recognition and internalization by glioblastoma cells. Finally, the signalling of tyrosine kinase receptors is involved in the peptide uptake, especially via EGFR overexpressed in tumour cells, indicating that the uptake of NFL-TBS.40-63 peptide by glioblastoma cells is related to their abnormally high proliferative activity.

URL de la noticehttp://okina.univ-angers.fr/publications/ua9037
DOI10.1016/j.ijpharm.2013.04.004
Lien vers le document

http://dx.doi.org/10.1016/j.ijpharm.2013.04.004