Open Access Research

Role of moesin in hyaluronan induced cell migration in glioblastoma multiforme

Leroi V DeSouza1, Ajay Matta1, Zia Karim1, Joydeep Mukherjee2, X Simon Wang1, Olga Krakovska1, Gelareh Zadeh2, Abhijit Guha2 and KW Michael Siu1*

Author Affiliations

1 Department of Chemistry and Centre for Research in Mass Spectrometry, York University, 4700 Keele Street, M3J 1P3, Toronto, Ontario, Canada

2 Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children Research Institute, University of Toronto, Toronto, Canada

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Molecular Cancer 2013, 12:74  doi:10.1186/1476-4598-12-74

Published: 15 July 2013

Abstract

Background

A major barrier to effective treatment of glioblastoma multiforme (GBM) is the invasion of glioma cells into the brain parenchyma rendering local therapies such as surgery and radiation therapy ineffective. GBM patients with such highly invasive and infiltrative tumors have poor prognosis with a median survival time of only about a year. However, the mechanisms leading to increased cell migration, invasion and diffused behavior of glioma cells are still poorly understood.

Methods

In the current study, we applied quantitative proteomics for the identification of differentially expressed proteins in GBMs as compared to non-malignant brain tissues.

Results

Our study led to the identification of 23 proteins showing overexpression in GBM; these include membrane proteins, moesin and CD44. The results were verified using Western blotting and immunohistochemistry in independent set of GBM and non-malignant brain tissues. Both GBM tissues and glioma cell lines (U87 / U373) demonstrated membranous expression of moesin and CD44, as revealed by immunohistochemistry and immunofluorescence, respectively. Notably, glioma cells transfected with moesin siRNA displayed reduced migration and invasion on treatment with hyaluronan (HA), an important component of the extracellular matrix in GBM. CD44, a transmembrane glycoprotein, acts as a major receptor for hyaluronan (HA). Using co-immunoprecipitation assays, we further demonstrated that moesin interacts with CD44 in glioma cells only after treatment with HA; this implicates a novel role of moesin in HA-CD44 signaling in gliomas.

Conclusions

Our results suggest that development of inhibitors which interfere with CD44-moesin interactions may open a new avenue in the future to mitigate cellular migration in gliomas.

Keywords:
Glioblastoma; CD44; ERM proteins; Moesin