Cadherin-11 regulates motility in normal cortical neural precursors and glioblastoma.
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.
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
Jessica D
JD
Schulte
Maya
M
Srikanth
Sunit
S
Das
Jianing
J
Zhang
Justin D
JD
Lathia
Lihui
L
Yin
Jeremy N
JN
Rich
Eric C
EC
Olson
John A
JA
Kessler
Anjen
A
Chenn
D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D034622:RNA Interference; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015820:Cadherins; D016212:Transforming Growth Factor beta; D049452:Green Fluorescent Proteins; C086960:osteoblast cadherin