title: Role of moesin in hyaluronan induced cell migration in glioblastoma multiforme.
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.
authors.affiliation: Department of Chemistry and Centre for Research in Mass Spectrometry, York University, 4700 Keele Street, M3J 1P3 Toronto, Ontario, Canada.
authors.forename: Leroi V
authors.initials: LV
authors.lastname: DeSouza
authors.forename: Ajay
authors.initials: A
authors.lastname: Matta
authors.forename: Zia
authors.initials: Z
authors.lastname: Karim
authors.forename: Joydeep
authors.initials: J
authors.lastname: Mukherjee
authors.forename: X Simon
authors.initials: XS
authors.lastname: Wang
authors.forename: Olga
authors.initials: O
authors.lastname: Krakovska
authors.forename: Gelareh
authors.initials: G
authors.lastname: Zadeh
authors.forename: Abhijit
authors.initials: A
authors.lastname: Guha
authors.forename: Kw Michael
authors.initials: KM
authors.lastname: Siu
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D020543:Proteome; D040901:Proteomics
chemical_list: D018960:Hyaluronan Receptors; D008840:Microfilament Proteins; D020543:Proteome; C071058:moesin; D006820:Hyaluronic Acid