Migration arrest in glioma cells is dependent on the alphav integrin subunit.
Local invasion is a hallmark of gliomas. Infiltrating tumor cells establish sites of persistent and recurrent lesions that ultimately prove fatal. Determinants of glioma cell migration include integrins and their ligands within the matrix. In contrast to the response to other matrix proteins, glioma cells migrating on tenascin do not follow a characteristic dose-dependent pattern. For two of four glioma cell lines tested, tenascin acts as both a permissive and a nonpermissive motility substrate, i.e., low densities of tenascin are permissive substrates, whereas high densities are nonpermissive. Specific antisense oligonucleotides directed at the alpha(v) integrin subunit effectively suppress the anti-migratory phenotype of glioma cells at high tenascin densities. The two cell lines that fail to demonstrate this unusual biphasic pattern do not endogenously express the alpha(v) subunit, whereas the cell lines for which high densities of tenascin are anti-migratory are found to express alpha(v). We conclude that loss of the alpha(v) integrin subunit may be associated with the invasive behavior of gliomas, along vascular channels that express tenascin.
Treasurywala
S
S
Barrow Neurological Institute, Saint Joseph's Hospital and Medical Center, Phoenix, Arizona 85013-4496, USA.
Berens
M E
ME
D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D015345:Oligonucleotide Probes; D051381:Rats; D017469:Receptors, Fibronectin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019063:Tenascin / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles
D015345:Oligonucleotide Probes; D017469:Receptors, Fibronectin; D019063:Tenascin; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue