title: Cadherin-11, a marker of the mesenchymal phenotype, regulates glioblastoma cell migration and survival in vivo.
abstract: Glioblastoma multiforme (GBM) is the most malignant and lethal form of astrocytoma. The GBM patient survival time of approximately 1 year necessitates the identification of novel molecular targets and more effective therapeutics. Cadherin-11, a calcium-dependent cell-cell adhesion molecule and mesenchymal marker, plays a role in both normal tissue development and in cancer cell migration. The functional significance of cadherin-11 in GBM has not been investigated. Here, we show that cadherin-11 is expressed in human GBM tumors and human glioma stem-like cells by immunohistochemical labeling. In addition, we show that cadherin-11 is expressed in human glioma cell lines by immunoblotting. Short hairpin RNA-mediated knockdown of cadherin-11 expression in human glioma cell lines results in decreased migration and growth factor-independent cell survival in vitro. More importantly, knockdown of cadherin-11 inhibits glioma cell survival in heterotopic and orthotopic mouse xenograft models. Together, our results show the functional significance of cadherin-11 expression in GBM and provide evidence for a novel role of cadherin-11 in promoting glioma cell survival in an in vivo environment. Thus, our studies suggest cadherin-11 is a viable molecular target for therapeutic intervention in GBM.
authors.affiliation: Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Kaur
authors.forename: Polly J
authors.initials: PJ
authors.lastname: Phillips-Mason
authors.forename: Susan M
authors.initials: SM
authors.lastname: Burden-Gulley
authors.forename: Amber E
authors.initials: AE
authors.lastname: Kerstetter-Fogle
authors.forename: James P
authors.initials: JP
authors.lastname: Basilion
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Sloan
authors.forename: Susann M
authors.initials: SM
authors.lastname: Brady-Kalnay
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010641:Phenotype; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C086960:osteoblast cadherin