Transmembrane protein 18 enhances the tropism of neural stem cells for glioma cells.
The failure of current glioma therapies is mainly due to the ability of the tumor cells to invade extensively the surrounding healthy brain tissue, hence escaping localized treatments. Neural stem cells (NSC) are able to home in on tumor foci at sites distant from the main tumor mass, possibly enabling treatment of scattered glioma clusters. To make the strategy more effective, we performed a cDNA expression library screening to identify the candidate genes that once overexpressed would enhance the tropism of NSCs for gliomas. Here, we show that a previously unannotated gene, the one encoding transmembrane protein 18 (TMEM18), is one such gene. Overexpression of TMEM18 was seen in the current study to provide NSCs and neural precursors an increased migration capacity toward glioblastoma cells in vitro and in the rat brain. Functional inactivation of the TMEM18 gene resulted in almost complete loss of the migration activity of these cells. Thus, TMEM18 is a novel cell migration modulator. Overexpression of this protein could be favorably used in NSC-based glioma therapy.
Institute of Bioengineering and Nanotechnology, Departments of Biological Sciences, National University of Singapore.
Jaana
J
Jurvansuu
Ying
Y
Zhao
Doreen S Y
DS
Leung
Jerome
J
Boulaire
Yuan Hong
YH
Yu
Sohail
S
Ahmed
Shu
S
Wang
D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D002465:Cell Movement; D017077:Culture Media, Conditioned; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015723:Gene Library; D020868:Gene Silencing; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018523:Tropism / Q000502:physiology*
D017077:Culture Media, Conditioned; D008565:Membrane Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C530715:TMEM18 protein, human