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PMID: 17968499 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Slit2 involvement in glioma cell migration is mediated by Robo1 receptor.

Journal of neuro-oncology ·Vol. 87 ·No. 1 ·2008-03-00 ·Pages 1-7

Mertsch S, Schmitz N, Jeibmann A, Geng JG, Paulus W, Senner V

Abstract

Slit and Robo proteins are evolutionarily conserved molecules whose interaction underlies axon guidance and neuronal precursor cell migration. During development secreted Slit proteins mediate chemorepulsive signals on cells expressing Robo receptors. Because similar molecular mechanisms may be utilized in glioma cell invasion and neuroblast migration, we studied the expression of Slit2 and its transmembrane receptor Robo1 as well as their functional role in migration in glioma cells. qRT-PCR and immunohistochemistry of human specimens revealed that Slit2 was distinctly expressed by non-neoplastic neurons, but at only very low levels in fibrillary astrocytoma and glioblastoma. Robo1 also was mainly restricted to neurons in the normal brain, whereas astrocytic tumor cells in situ as well as glioblastoma cell lines overexpressed Robo1 at mRNA and protein levels. Recombinant human Slit2 in a concentration of 0.45 nM was repulsive for glioma cell lines in a modified Boyden chamber assay. RNAi-mediated knockdown of Robo1 in glioma cell lines neutralized the repulsive effect of Slit2, demonstrating that Robo1 served as the major Slit2 receptor. Our findings suggest that a chemorepulsive effect mediated by interaction of Slit2 and Robo1 participates in glioma cell guidance in the brain.

MeSH Terms
Astrocytes/metabolism Blotting, Western Brain Neoplasms/metabolism Cell Line, Tumor Cell Movement/physiology Fluorescent Antibody Technique Glioma/metabolism Humans Immunohistochemistry Intercellular Signaling Peptides and Proteins/metabolism Nerve Tissue Proteins/metabolism Neurons/metabolism RNA, Small Interfering Receptors, Immunologic/metabolism Reverse Transcriptase Polymerase Chain Reaction
Chemicals
Intercellular Signaling Peptides and Proteins Nerve Tissue Proteins RNA, Small Interfering Receptors, Immunologic roundabout protein Slit homolog 2 protein
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Mertsch Sonja
Institute of Neuropathology, University Hospital Münster, Domagkstr. 19, 48149, Münster, Germany.
Schmitz Nicole
Jeibmann Astrid
Geng Jian-Guo
Paulus Werner
Senner Volker
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Article Info
Journal
Journal of neuro-oncology
Abbr.
J Neurooncol
ISSN
0167-594X
DOI
10.1007/s11060-007-9484-2
Published
2008-03-00
Epub
2007-00-30
Pages
1-7
Language
English
Region
United States
NLM ID
8309335
Subset
IM
External Links
PubMed source DOI: 10.1007/s11060-007-9484-2 View journal details
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