Role of moesin in hyaluronan induced cell migration in glioblastoma multiforme

Molecular Cancer

Research

Joydeep Mukherjee¹  Abhijit Guha¹  Gelareh Zadeh¹  X Simon Wang²  Ajay Matta²  KW Michael Siu²  Zia Karim²  Leroi V DeSouza²  Olga Krakovska² 

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

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

关键词: Glioblastoma;    CD44;    ERM proteins;    Moesin;   

DOI  :  10.1186/1476-4598-12-74

 received in 2013-03-25, accepted in 2013-06-25,  发布年份 2013

来源: Springer

【 摘 要 】

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

【 授权许可】

Unknown   
© DeSouza et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.