Hyaluronate receptors mediating glioma cell migration and proliferation

Citation
Y. Akiyama et al., Hyaluronate receptors mediating glioma cell migration and proliferation, J NEURO-ONC, 53(2), 2001, pp. 115-127
Citations number
71
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
JOURNAL OF NEURO-ONCOLOGY
ISSN journal
0167-594X → ACNP
Volume
53
Issue
2
Year of publication
2001
Pages
115 - 127
Database
ISI
SICI code
0167-594X(2001)53:2<115:HRMGCM>2.0.ZU;2-J
Abstract
The extracellular matrix (ECM) of the central nervous system (CNS) is enric hed in hyaluronate (HA). Ubiquitous receptors for HA are CD44 and the Recep tor for HA-Mediated Motility known as RHAMM. In the present study, we have investigated the potential role of CD44 and RHAMM in the migration and prol iferation of human astrocytoma cells. HA-receptor expression in brain tumor cell lines and surgical specimens was determined by immunocytochemistry an d western blot analyses. The ability of RHAMM to bind ligand was determined through cetylpyridinium chloride (CPC) precipitations of brain tumor lysat es in HA-binding assays. The effects of HA, CD44 blocking antibodies, and R HAMM soluble peptide on astrocytoma cell growth and migration was determine d using MTT and migration assays. Our results show that the expression of t he HA-receptors, CD44, and RHAMM, is virtually ubiquitous amongst glioma ce ll lines, and glioma tumor specimens. There was a gradient of expression am ongst gliomas with high grade gliomas expressing more RHAMM and CD44 than d id lower grade lesions or did normal human astrocytes or non-neoplastic spe cimens of human brain. Specific RHAMM variants of 85- and 58-kDa size were shown to bind avidly to HA following CPC precipitations. RHAMM soluble pept ide inhibited glioma cell line proliferation in a dose-dependent fashion. F inally, while anti-CD44 antibodies did not inhibit the migration of human g lioma cells, soluble peptides directed at the HA-binding domain of RHAMM in hibited glioma migration both on and off an HA-based ECM. These data suppor t the notion that HA-receptors contribute to brain tumor adhesion, prolifer ation, and migration, biological features which must be better understood b efore more effective treatment strategies for these tumors can be found.