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Updated: Oct 11, 2026

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
Published on: August 25, 2023
MYCN-related suppression of functional CD44 expression enhances tumorigenic properties of human neuroblastoma cells
N Gross1, K Balmas Bourloud, C B Brognara
1Onco-Hematology Unit, University Hospital CHUV, Lausanne, 1011, Switzerland. Nicole.Gross@chuv.hospvd.ch
Abstract:
Highly malignant neuroblastoma tumors with MYCN amplification have been shown to downregulate the expression of the CD44 adhesion receptor. We have previously shown that MYCN amplified neuroblastoma cell lines either lack CD44 expression or express a nonfunctional, nonhyaluronic acid-binding CD44 receptor. By analysis of cells with manipulated expression of either CD44 or MYCN, we demonstrate that transfection of cells with a CD44 full-length cDNA construct produced a functional receptor in single copy MYCN cells and a nonfunctional CD44 receptor in MYCN amplified cells, similar to the CD44 receptor expressed by cells with enforced MYCN. Analysis of the in vivo growth properties of the transfectants revealed that the restoration of a functional CD44 receptor in nonamplified cells resulted in the suppression of in vivo cell growth, therefore linking the MYCN-related lack of hyaluronic acid-binding function of CD44 to the highly tumorigenic properties of a subset of neuroblastoma cells.
Insights
Neuroblastoma tumors with MYCN amplification often lack functional CD44 receptors, hindering hyaluronic acid binding. Restoring CD44 function in non-amplified cells suppressed tumor growth, linking CD44 dysfunction to neuroblastoma malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Cell Adhesion
Background:
- Highly malignant neuroblastomas often exhibit MYCN amplification.
- MYCN amplification is associated with downregulated CD44 adhesion receptor expression.
- Previously, MYCN-amplified neuroblastoma cells showed absent or nonfunctional CD44 receptors.
Purpose of the Study:
- To investigate the functional consequences of CD44 receptor expression in neuroblastoma.
- To determine the relationship between MYCN amplification, CD44 function, and tumor growth.
- To link CD44 hyaluronic acid-binding deficiency to neuroblastoma tumorigenicity.
Main Methods:
- Transfection of neuroblastoma cell lines with a full-length CD44 cDNA construct.
- Manipulation of MYCN expression levels in neuroblastoma cells.
- Analysis of CD44 receptor function (hyaluronic acid binding) and in vivo growth properties.
Main Results:
- Transfection yielded functional CD44 in single-copy MYCN cells but nonfunctional CD44 in MYCN-amplified cells.
- Enforced MYCN expression mimicked the nonfunctional CD44 phenotype.
- Restoration of functional CD44 in non-amplified cells suppressed in vivo tumor growth.
Conclusions:
- MYCN amplification leads to a nonfunctional CD44 receptor in neuroblastoma.
- The loss of CD44 hyaluronic acid-binding function contributes to the high tumorigenicity of MYCN-amplified neuroblastomas.
- Targeting CD44 function may offer therapeutic strategies for neuroblastoma.
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