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Related Experiment Video

Updated: Mar 25, 2026

Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma
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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.

EMBO Molecular Medicine
|February 17, 2016
PubMed
Summary

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.

Keywords:
DCCapoptosisdependence receptorsnetrin‐1non‐Hodgkin lymphoma

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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.