Cadherin-11 regulates motility in normal cortical neural precursors and glioblastoma

• Published in: PloS one 2013-08, Vol.8 (8), p.e70962-e70962
• Main Authors: Schulte, Jessica D, Srikanth, Maya, Das, Sunit, Zhang, Jianing, Lathia, Justin D, Yin, Lihui, Rich, Jeremy N, Olson, Eric C, Kessler, John A, Chenn, Anjen
• Format: Article
• Language: English
• Subjects: Animals; Biology; Blotting, Western; Brain; Brain cancer; Brain research; Brain tumors; Cadherins; Cadherins - genetics; Cadherins - metabolism; Cell adhesion & migration; Cell migration; Cell Movement - drug effects; Cell Movement - genetics; Cell survival; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Cerebral Cortex - metabolism; Cortex; Cytoskeleton; Endothelial cells; Epithelial cells; Female; Fluorescent Antibody Technique; Gene expression; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastoma cells; Glioblastomas; Glioma; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Kinases; Male; Medical prognosis; Medicine; Mesenchyme; Mice, Inbred C57BL; Mice, Transgenic; Morphology; Motility; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Neural stem cells; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurology; Neurons; Pathology; Precursors; Pregnancy; Proteins; RNA Interference; Signaling; Stem cells; Transformation; Transforming Growth Factor beta - pharmacology; Transforming growth factors; Tumor cells; Tumor Cells, Cultured; Tumors; Ventricle; Ventricular zone
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0070962

Metastasizing tumor cells undergo a transformation that resembles a process in normal development when non-migratory epithelial cells modulate the expression of cytoskeletal and adhesion proteins to promote cell motility. Here we find a mesenchymal cadherin, Cadherin-11 (CDH11), is increased in cells exiting the ventricular zone (VZ) neuroepithelium during normal cerebral cortical development. When overexpressed in cortical progenitors in vivo, CDH11 causes premature exit from the neuroepithelium and increased cell migration. CDH11 expression is elevated in human brain tumors, correlating with higher tumor grade and decreased patient survival. In glioblastoma, CDH11-expressing tumor cells can be found localized near tumor vasculature. Endothelial cells stimulate TGFβ signaling and CDH11 expression in glioblastoma cells. TGFβ promotes glioblastoma cell motility, and knockdown of CDH11 expression in primary human glioblastoma cells inhibits TGFβ-stimulated migration. Together, these findings show that Cadherin-11 can promote cell migration in neural precursors and glioblastoma cells and suggest that endothelial cells increase tumor aggressiveness by co-opting mechanisms that regulate normal neural development.