Inhibition of medulloblastoma cell invasion by Slit.
Invasion of brain tumor cells has made primary malignant brain neoplasms among the most recalcitrant to therapeutic strategies. We tested whether the secreted protein Slit2, which guides the projection of axons and developing neurons, could modulate brain tumor cell invasion. Slit2 inhibited the invasion of medulloblastoma cells in a variety of in vitro models. The effect of Slit2 was inhibited by the Robo ectodomain. Time-lapse videomicroscopy indicated that Slit2 reduced medulloblastoma invasion rate without affecting cell direction or proliferation. Both medulloblastoma and glioma tumors express Robo1 and Slit2, but only medulloblastoma invasion is inhibited by recombinant Slit2 protein. Downregulation of activated Cdc42 may contribute to this differential response. Our findings reinforce the concept that neurodevelopmental cues such as Slit2 may provide insights into brain tumor invasion.
Werbowetski-Ogilvie
T E
TE
Brain Tumour Research Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Seyed Sadr
M
M
Jabado
N
N
Angers-Loustau
A
A
Agar
N Y R
NY
Wu
J
J
Bjerkvig
R
R
Antel
J P
JP
Faury
D
D
Rao
Y
Y
Del Maestro
R F
RF
D000818:Animals; D001254:Astrocytoma / Q000235:genetics / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000473:pathology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D005910:Glioma / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008527:Medulloblastoma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D018715:Microscopy, Video; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D012334:RNA, Neoplasm; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein