Contactin is expressed in human astrocytic gliomas and mediates repulsive effects.
Contactin is a cell surface adhesion molecule that is normally expressed by neurons and oligodendrocytes. Particularly high levels of contactin are present during brain development. Using subtractive cloning, we identified contactin transcripts as overexpressed in glioblastomas compared with normal brain. We confirmed contactin overexpression in glioblastomas at the protein level, and localized contactin to the surface of glial fibrillary acidic protein (GFAP)-expressing glioblastoma cells. In contrast, normal astrocytes did not express contactin. Analyzing different types of astrocytic tumors, we detected an association between increasing malignancy grade and contactin expression. Functionally, contactin had repellent effects on glioma cells in vitro, as demonstrated by adhesion and migration assays. Overexpression of contactin by transfection into glioblastoma cells did not alter the proliferation rate or adhesion to various extracellular matrix proteins as well as adhesion to cells expressing the specific contactin ligand the protein tyrosine phosphatase zeta (PTPzeta). Our findings suggest that contactin has repellent effects on glioma cells to which it is presented as a ligand, but it does not alter the proliferative or adhesive capacities of cells that overexpress the molecule. The repulsive properties of contactin may be a key factor in glioma disaggregation, and may contribute to the diffuse infiltration pattern characteristic of glioma cells in human brain.
Eckerich
Carmen
C
Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Zapf
Svenja
S
Ulbricht
Ulrike
U
Müller
Sabine
S
Fillbrandt
Regina
R
Westphal
Manfred
M
Lamszus
Katrin
K
D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002449:Cell Aggregation / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D058966:Contactins; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009361:Neoplasm Invasiveness; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism
D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D016326:Extracellular Matrix Proteins; D005904:Glial Fibrillary Acidic Protein; D008024:Ligands; D017027:Protein Tyrosine Phosphatases