αB-crystallin is elevated in highly infiltrative apoptosis-resistant glioblastoma cells

Dorota Goplen*, Sébastien Bougnaud, Uroš Rajcevic, Stig O. Bøe, Kai O. Skaftnesmo, Juergen Voges, Per O.Ø. Enger, Jian Wang, Berit B. Tysnes, Ole D. Laerum, Simone Niclou, Rolf Bjerkvig

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

39 Citations (Scopus)

Abstract

We have previously established two distinct glioma phenotypes by serial xenotransplantation of human glioblastoma (GBM) biopsies in nude rats. These tumors undergo a gradual transition from a highly invasive nonangiogenic to a less-invasive angiogenic phenotype. In a protein screen to identify molecular markers associated with the infiltrative phenotype, we identified α-basic-crystallin (αBc), a small heatshock protein with cytoprotective properties. Its increased expression in the infiltrative phenotype was validated by immunohistochemistry and Western blots, confirming its identity to be tumor-derived and not from the host. Stereotactic human GBM biopsies taken from MRI-defined areas verified stronger αBc expression in the infiltrative edge compared to the tumor core. Cell migration assays and immunofluorescence staining showed αBc to be expressed by migrating cells in vitro. To determine αBc function, we altered its expression levels. αBc siRNA depletion caused a loss of migrating tumor cells from biopsy spheroids and delayed monolayer wound closure. In contrast, glioma cell migration in a Boyden chamber assay was unaffected by either αBc knockdown or overexpression, indicating that αBc is not functionally linked to the cell migration machinery. However, after siRNA αBc depletion, a significant sensitization of cells to various apoptotic inducers was observed (actinomycin, tumor necrosis factor α, and TNF-related apoptosis-inducing ligand [TRAIL]). In conclusion, αBc is overexpressed by highly migratory glioma cells where it plays a functional role in apoptosis resistance.

Original languageEnglish
Pages (from-to)1618-1628
Number of pages11
JournalAmerican Journal of Pathology
Volume177
Issue number4
DOIs
Publication statusPublished - Oct 2010

Fingerprint

Dive into the research topics of 'αB-crystallin is elevated in highly infiltrative apoptosis-resistant glioblastoma cells'. Together they form a unique fingerprint.

Cite this