MYCN-related suppression of functional CD44 expression enhances tumorigenic properties of human neuroblastoma cells

Highly malignant neuroblastoma tumors with MYCN amplification have been sho wn to downregulate the expression of the CD44 adhesion receptor. We have pr eviously shown that MYCN amplified neuroblastoma cell lines either lack CD4 4 expression or express a nonfunctional, nonhyaluronic acid binding CD44 re ceptor. By analysis of cells with manipulated expression of either CD44 or MYCN, we demonstrate that transfection of cells with a CD44 full-length cDN A construct produced a functional receptor in single copy MYCN cells and a nonfunctional CD44 receptor in MYCN amplified cells, similar to the CD44 re ceptor expressed by cells with enforced MYCN. Analysis of the in vivo growt h properties of the transfectants revealed that the restoration of a functi onal CD44 receptor in nonamplified cells resulted in the suppression of in vivo cell growth, therefore linking the MYCN-related lack of hyaluronic aci d-binding function of CD44 to the highly tumorigenic properties of a subset of neuroblastoma cells. (C) 2000 Academic Press.