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Updated: Mar 25, 2026
Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma
Published on: March 30, 2018
Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas
Laura Broutier1, Marion Creveaux1, Jonathan Vial1
1Dependence Receptors, Cancer and Development Laboratory - Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286 Université de Lyon Centre Léon Bérard, Lyon, France.
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.
Insights
The Deleted in Colorectal Carcinoma (DCC) protein suppresses tumors by inducing apoptosis, but its role in lymphoma was unclear. This study shows netrin-1 interference with DCC promotes lymphoma, suggesting a new therapeutic target for DLBCL and MCL.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- The Deleted in Colorectal Carcinoma (DCC) receptor normally suppresses tumor growth by inducing apoptosis.
- Its tumor suppressive function is well-documented in breast and colorectal cancers but not established in other malignancies.
- Netrin-1 binding to DCC inhibits this apoptosis, promoting tumor progression.
Purpose of the Study:
- To investigate the role of the netrin-1/DCC pathway in lymphomagenesis.
- To determine if DCC-induced apoptosis inhibition is linked to lymphoma development.
- To explore netrin-1 as a potential therapeutic target in specific lymphoma subtypes.
Main Methods:
- Utilized a transgenic mouse model to study lymphomagenesis associated with DCC.
- Analyzed the netrin-1/DCC ratio in human diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) samples.
- Employed a netrin-1 interfering antibody for in vitro and in vivo experiments.
Main Results:
- Inhibition of DCC-induced apoptosis correlated with lymphomagenesis in the mouse model.
- Human DLBCL (germinal center and ABC subtypes) and MCL exhibited an imbalanced netrin-1/DCC ratio.
- Netrin-1 was confirmed as a survival factor for ABC-DLBCL and MCL tumor cells.
Conclusions:
- The netrin-1/DCC interaction plays a critical role in lymphoma development.
- Netrin-1 acts as a survival factor for specific lymphoma subtypes.
- Targeting the netrin-1/DCC interaction with antibodies offers a potential therapeutic strategy for netrin-1-positive DLBCL and MCL.
