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

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.