Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas.
EMBO Mol Med
; 8(2): 96-104, 2016 Feb 01.
Article
in En
| MEDLINE
| ID: mdl-26882243
ABSTRACT
DCC (Deleted in Colorectal Carcinoma) has been demonstrated to constrain tumor progression by inducing apoptosis unless engaged by its ligand netrin-1. This has been shown in breast and colorectal cancers; however, this tumor suppressive function in other cancers is not established. Using a transgenic mouse model, we report here that inhibition of DCC-induced apoptosis is associated with lymphomagenesis. In human diffuse large B-cell lymphoma (DLBCL), an imbalance of the netrin-1/DCC ratio suggests a loss of DCC-induced apoptosis, either via a decrease in DCC expression in germinal center subtype or by up-regulation of netrin-1 in activated B-cell (ABC) one. Such imbalance is also observed in mantle cell lymphoma (MCL). Using a netrin-1 interfering antibody, we demonstrate both in vitro and in vivo that netrin-1 acts as a survival factor for ABC-DLBCL and MCL tumor cells. Together, these data suggest that interference with the netrin-1/DCC interaction could represent a promising therapeutic strategy in netrin-1-positive DLBCL and MCL.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphoma, Large B-Cell, Diffuse
/
Receptors, Cell Surface
/
Lymphoma, Mantle-Cell
/
Tumor Suppressor Proteins
/
Nerve Growth Factors
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
EMBO Mol Med
Journal subject:
BIOLOGIA MOLECULAR
Year:
2016
Document type:
Article
Affiliation country:
Francia