Absence of functional CD44 hyaluronan receptor on human NMYC-amplified neuroblastoma cells

Détails

ID Serval
serval:BIB_C5A981B84635
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Absence of functional CD44 hyaluronan receptor on human NMYC-amplified neuroblastoma cells
Périodique
Cancer Research
Auteur(s)
Gross  N., Balmas  K., Brognara  C. B.
ISSN
0008-5472
Statut éditorial
Publié
Date de publication
04/1997
Peer-reviewed
Oui
Volume
57
Numéro
7
Pages
1387-93
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr 1
Résumé
CD44 represents a heterogeneous group of surface glycoproteins, involved in cell-cell and cell-matrix interactions. CD44 is the major receptor for hyaluronate (HA), a component of cell matrices, and most of CD44 known functions are attributed to its ability to recognize HA. We have recently shown that although a majority of human neuroblastomas (NBs), a childhood cancer, express high levels of CD44H, high stages and tumors with amplification of the NMYC proto-oncogene fail to express CD44. Lack of CD44 expression is strongly associated with the presence of NMYC amplification and has been further shown to represent a new feature for predicting risk of disease progression and dissemination. In the present study, we have investigated the role of CD44 expressed by NB cell lines and the possible relationship among the presence of NMYC amplification, functional expression of CD44 receptor, and tumorigenic properties of NB cells. A panel of cell lines with variable NMYC amplification and/or overexpression, as well as clonal and stable NMYC-transfected NB cells, were analyzed for CD44 expression and ability to bind HA. Our results confirmed previous observations that in NB cell lines lack of CD44 is not always related to the presence of NMYC amplification, with a number of cell lines or transfectants with both CD44 expression and NMYC amplification. However, the ability of the CD44 receptor to bind immobilized hyaluronan was restricted to CD44H+ cell lines without NMYC amplification (SH-EP and ACN). The HA-binding function was CD44 dependent and could be specifically blocked by an anti-CD44 antibody. No induction of functional HA binding was obtained with NMYC-amplified cell lines or NMYC transfectants, despite an induced increase of CD44 expression upon differentiation or after tentative activation of the receptor with phorbol esters. Inhibition of N-linked glycosylation with tunicamycin resulted in decreased HA binding of cells bearing an active CD44 receptor. We conclude that NMYC-amplified NB cell lines either do not express CD44 at all or express a nonfunctional receptor, whereas nonamplified cells constitutively express an active receptor. The lack of functional HA binding in NB cells might be partly due to incomplete N-glycosylation. The involvement of NMYC in the regulation of N-linked glycosylation can be suspected.
Mots-clé
Antibodies, Blocking/pharmacology Antigens, CD44/*metabolism Cell Adhesion/drug effects/physiology Collagen/metabolism Fibronectins/metabolism Genes, myc/*genetics Humans Hyaluronic Acid/*metabolism Hyaluronoglucosaminidase/pharmacology Laminin/metabolism Neuroblastoma/*metabolism Time Factors Transfection Tunicamycin/pharmacology
Pubmed
Web of science
Création de la notice
20/01/2008 16:55
Dernière modification de la notice
03/03/2018 21:16
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