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PMID: 11716065 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Hyaluronate receptors mediating glioma cell migration and proliferation.

Journal of neuro-oncology ·Vol. 53 ·No. 2 ·2001-06-00 ·Pages 115-27

Akiyama Y, Jung S, Salhia B, Lee S, Hubbard S, Taylor M, Mainprize T, Akaishi K, van Furth W, Rutka JT

Abstract

The extracellular matrix (ECM) of the central nervous system (CNS) is enriched in hyaluronate (HA). Ubiquitous receptors for HA are CD44 and the Receptor 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 proliferation of human astrocytoma cells. HA-receptor expression in brain tumor cell lines and surgical specimens was determined by immunocytochemistry and western blot analyses. The ability of RHAMM to bind ligand was determined through cetylpyridinium chloride (CPC) precipitations of brain tumor lysates in HA-binding assays. The effects of HA, CD44 blocking antibodies, and RHAMM soluble peptide on astrocytoma cell growth and migration was determined using MTT and migration assays. Our results show that the expression of the HA-receptors, CD44, and RHAMM, is virtually ubiquitous amongst glioma cell lines, and glioma tumor specimens. There was a gradient of expression amongst gliomas with high grade gliomas expressing more RHAMM and CD44 than did lower grade lesions or did normal human astrocytes or non-neoplastic specimens of human brain. Specific RHAMM variants of 85- and 58-kDa size were shown to bind avidly to HA following CPC precipitations. RHAMM soluble peptide inhibited glioma cell line proliferation in a dose-dependent fashion. Finally, while anti-CD44 antibodies did not inhibit the migration of human glioma cells, soluble peptides directed at the HA-binding domain of RHAMM inhibited glioma migration both on and off an HA-based ECM. These data support the notion that HA-receptors contribute to brain tumor adhesion, proliferation, and migration, biological features which must be better understood before more effective treatment strategies for these tumors can be found.

MeSH Terms
Antibodies, Monoclonal/pharmacology Astrocytoma/metabolism,pathology Blotting, Western Brain Neoplasms/metabolism,pathology Cell Division Cell Movement Extracellular Matrix/metabolism Extracellular Matrix Proteins/immunology,physiology Ganglioglioma/metabolism,pathology Glioblastoma/metabolism,pathology Glioma/metabolism,pathology Hyaluronan Receptors/immunology,physiology Hyaluronic Acid/metabolism Medulloblastoma/metabolism,pathology Microscopy, Fluorescence Molecular Weight Neoplasm Invasiveness/physiopathology Neoplasm Proteins/immunology,physiology Tumor Cells, Cultured
Chemicals
Antibodies, Monoclonal Extracellular Matrix Proteins Hyaluronan Receptors Neoplasm Proteins hyaluronan-mediated motility receptor Hyaluronic Acid
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Akiyama Y
Arthur and Sonia Labatt Brain Tumor Research Centre and the Division of Neurosurgery The Hospital for Sick Children, University of Toronto, Ontario, Canada.
Jung S
Salhia B
Lee S
Hubbard S
Taylor M
Mainprize T
Akaishi K
van Furth W
Rutka J T
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Article Info
Journal
Journal of neuro-oncology
Abbr.
J Neurooncol
ISSN
0167-594X
DOI
10.1023/a:1012297132047
Published
2001-06-00
Pages
115-27
Language
English
Region
United States
NLM ID
8309335
Subset
IM
External Links
PubMed source DOI: 10.1023/a:1012297132047 View journal details
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